Skip to main content

Mechanisms involved in the anticancer effects of sinapic acid



Cancer refers to a group of diseases characterized by the development of abnormal cells that divide uncontrollably and have the ability to infiltrate and destroy normal body tissue. Worldwide, it is the second most leading cause of death. Dietary intake of bioactive compounds from plant sources has been documented for their protective effect against different types of human ailments including cancer.

Main body

Sinapic acid (3,5-dimethoxy-4-hydroxycinnamic acid) (SA) is a promising phytochemical, available in oil seeds, berries, spices, vegetables and cereals. SA has been well documented for its antibacterial, anti-peroxidative, anti-hyperglycemic, anticancer, hepatoprotective, reno-protective, anti-inflammatory, neuroprotective, immunomodulatory and anticancer effects. Nevertheless, the anticancer activity of SA has remained a challenge with regard to understanding its mechanism in health and diseases.

Short conclusion

This review is an effort to summarize the updated literature available about the mechanisms involved in the anticancer effects of SA in order to recommend this compound for further future investigations.


Cancer is a deadly disease caused by abnormal cell growth with aggressive potentials (Hausman 2019). Several reports have shown that cancer incidence and deaths are due to various environmental and genetic factors such as heredity, decreased intake of plant-based products, excessive body mass index, absence of physical activity, increased tobacco use, alcohol addiction, severe radiation exposure and uncontrolled infections (Iranda-Galvis et al. 2021; Willenbrink et al. 2020). Application of dietary phytochemicals has been considered to be a novel and therapeutic approach to treat variety of tumors on the basis of their mechanism of action (Al-Ishaq et al. 2020; Mao et al. 2020).

In recent years, many studies have reported that foods enriched with polyphenols have the potential to protect against various disorders like, diabetes mellitus, hepatic disorders, cardiovascular disease, cancer, arthritis, Alzheimer’s disease and many more (Bungau et al. 2019; Fraga et al. 2019). Findings from various studies have proved that plant-derived compounds are found to be non-toxic when taken in smaller quantities and they possess exceptional therapeutic effects (de Lima Cherubim et al. 2020; Bracci et al. 2021). Sinapic acid (SA) is one such polyphenol that is reported to show several health promoting activities.

Sinapic acid (SA), a cinnamic acid derivative is predominantly found in the plant kingdom. It is chemically 3,5‐dimethoxy‐4‐hydroxycinnamic acid and is present in rye, fruits and vegetables (Niciforovic and Abramovic 2014; Russell et al. 2009) (Fig. 1). SA is seen as a yellow–brown crystalline powder. It has a molecular weight of 224.21 g/mol. The melting point of SA is 203–205 °C, and it is found to be incompatible with strong oxidizing agents and strong bases. Studies have shown that SA is poorly soluble in water, but soluble in carbitol and freely soluble in DMSO (Hosny et al. 2018).

Fig. 1
figure 1

Structure of sinapic acid

Importance of SA

SA has been reported to possess various beneficial activities. SA is demonstrated to be a vital chain-breaking antioxidant that efficiently functions as radical scavenger (Gaspar et al. 2010). SA is also reported to show potent hepatoprotective activity against several toxic agents (Shin et al. 2013a, b). Studies have reported the beneficial effect of SA on cisplatin-induced nephrotoxicity (Ansari 2017). The neuroprotective function of SA in Alzheimer’s disease is also investigated (Lee et al. 2012). Many studies have reported the effective anti-hyperglycemic and antidiabetic role of SA against experimental diabetes (Cherng et al. 2013). Other than this, anti-inflammatory (Lee 2018), anticancer (Huang et al. 2021), cardioprotective (Bin Jardan et al. 2020) and anxiolytic effects (Yoon et al. 2007) of SA are also reported.

The pharmacological effects of SA have been extensively documented over the past few decades. In this review, we discuss the molecular mechanisms involved in the anticancer effect of SA.

Main text

Bioavailability and metabolism

Studies have shown that the bioavailability of SA has been potentially significant and it is dependent on its solubility in different medium. Reports on SA metabolism indicated the presence of SA and their conjugates in urine (Shirley and Chapple 2003). SA can be efficiently stored and transported in blood by albumin; this was confirmed by UV absorption spectrometry and fluorescence quenching method (Markovic et al. 2005). Various pre-clinical studies have shown that SA is well tolerated and oral tolerance of SA was appreciable (Alaofi 2020; Shin et al. 2013a, b; Roy and Maizen Prince 2013).

Mechanisms involved in the anticancer activity of SA

Anti-tumorigenic and chemopreventive effects of SA

Balaji et al. reported the anticancer role of SA on 1,2 dimethyl hydrazine (DMH) in Wistar rats (Balaji et al. 2014). DMH was given at a dose of 20 mg/kg body weight subcutaneously to induce colon cancer in rats. SA was supplemented through oral gavage route at different doses (20, 40, 60 and 80 mg/kg body weight) for 16 weeks to study its effect. SA treatment reduced the incidence of polyp up to 66.66% and prevented the DMH-induced histological abnormalities such as dysplasia, enlarged nuclei and densely packed inflammatory cell infiltrates and lymphoid aggregates in colon. In another study (Balaji et al. 2015) on colon cancer, oral administration of SA up to 80 mg/kg body weight reduced the number of aberrant crypt foci up to 34.55% compared to the DMH-induced colon cancer-induced group (58.83%). Anti-tumor effect of SA on dimethyl benz(a)anthracene (DMBA)-induced experimental oral cancer was reported in Syrian hamsters (Kalaimathi and Suresh 2015a). SA was administered orally (50 mg/kg body weight) for 16 weeks. The incidence of oral cancer was 100% in DMBA-induced group that was reduced to 20% in SA-supplemented animals. SA treatment also reduced tumor volume and ameliorated the histological changes such as hyperkeratosis, hyperplasia, thickened epithelial layer and keratin pearl formation induced by DMBA. All these findings support the anti-tumorigenic and chemopreventive effects of SA.

SA modulates cellular redox homeostasis

Free radical and non-radical oxidizing species (reactive oxygen species) (ROS) are commonly elevated in cancerous conditions and reports suggest that these free radicals and electrophiles mediated oxidative stress have an important role in all stages of chemical carcinogenesis and tumorigenesis (Anandakumar et al. 2008). These toxic radicals are involved in inducing cellular lipid peroxidation (LPO) that disturb the cellular redox homeostasis. SA has the ability to reduce carcinogenic burden by its potent anti-peroxidative efficacy by strengthening the cellular antioxidant defense system. Balaji et al. (2015) have reported that the levels of serum thiobarbituric acid substances (TBARS) and conjugated dienes (CDs) were increased (1.5-fold and 0.5-fold) in the DMBA-induced colon cancer in rats; the levels/activities of antioxidants like SOD, CAT, GPX, GST, GR, GSH, vitamin C and vitamin E were also decreased in colon cancer-bearing rats. Supplementation of SA was found to be effective in improving the abnormalities induced by DMBA. Another study also reported the ability of SA to improve cellular antioxidants against lung cancer (Hu et al. 2021). Tungalag et al. (2021) showed that the expression of antioxidant proteins such as SOD1, SOD2 and CAT were significantly increased upon SA treatment in SH-SY5Y human neuroblastoma cells. Other than its potent antioxidant function, SA also possesses pro-oxidant effect that has been identified to affect the redox state of tumor cells (Martin-Cordero et al. 2012). Due to increased alterations in their metabolism and signaling pathways, cancer cells produce high amount of ROS that results in a state of increased basal oxidative stress (Shah and Rogoff 2021). At this state, cancer cells become highly susceptible to pro-oxidant agents that enhance the production of ROS to a level where they become cytotoxic. SA at higher concentrations acts as a potent pro-oxidant agent, resulting in increased generation of free radicals. Janakiraman et al. (2014) reported this effect of SA in human laryngeal carcinoma cell line (HEp-2). SA-treated cells showed increased ROS levels in the treated cells (108.32 ± 7.32) compared to untreated cells (76.41 ± 7.09) (Janakiraman et al. 2014). Hu et al. (2021) reported that in human lung A549 cells, SA (50 and 75 μM) increased ROS accumulation in the treated cells compared to the untreated cells. Similar results were reported by Badr et al. (2019) in A549 and Caco-2 cancer cell lines.

Effect of SA on liver biotransformation enzymes and intestinal bacterial enzyme activity

The activity of biotransformation enzymes plays a critical role in the activation as well as elimination of carcinogens. While phase I enzymes are responsible for the activation of pro-carcinogen to its active carcinogen, phase II enzymes are involved in the conjugation of such compounds, making them more water soluble and excretable. Balaji et al. (2014) studied the modulatory effect of SA on biotransformation enzymes in rat colon cancer, and Kalaimathi and Suresh (2015a, b) also reported the modifying effect of SA on phase I and II enzymes in rat buccal carcinogenesis. In all these studies, the activities of liver phase I biotransformation enzymes like CYP450 and CYP2E1 were markedly increased and the activities of phase II biotransformation enzymes such as glutathione-S-transferase (GST), DT-diaphorase (DTD) and UDP-glucuronyl transferase (UDP-GT) were markedly decreased in cancer-bearing animals on SA treatment. The activities of biotransformation enzymes were reinstated to near normal levels in both the studies.

The intestinal bacterial enzymes play a significant part in the pathogenesis of several cancers (Jackson and Theiss 2020). These enzymes are responsible for activating the metabolism of carcinogens and tumor promoters in the colon. Additionally, the toxic and genotoxic metabolites produced by the intestinal microflora may bind to the particular intestinal cell surface receptors and regulate intracellular signal transduction. Balaji et al. (2015) have reported the influence of SA on regulating the intestinal bacterial enzyme activity in a rat colon cancer model. The activities of fecal bacterial enzymes such as β-glucuronidase, β-glucosidase, β-galactosidase, nitro-reductase, sulfatase and mucinase were modulated in SA-treated animals.

Effect of SA on serum marker enzymes

LPO-induced tissue damage is the sensitive feature in the cancerous conditions and any damage to membrane may result in the leakage of these enzymes from the tissues (Scandolara et al. 2022). Cancer chemoprevention and therapy depends on the investigation of these marker enzymes. Hu et al. (2021) have studied the effect of SA on changes in the levels of serum marker enzymes in benzo(a)pyrene (B(a)P) induced lung cancer in mice. The levels of serum CEA, AHH, LDH, GGT, and 5’NT were abnormally raised in the B(a)P-induced lung cancer-bearing mice. These changes in the serum enzymes were reinstated in the SA (30 mg/kg body weight)-treated mice.

Effect of SA on hematology and immunoglobulins

Hematological abnormalities are commonly found in cancer. The most common one being anemia because of acute or chronic blood loss, marrow involvement by the malignancy, marrow suppressive effects of chemotherapy or radiation therapy (Yoshida et al. 2022). Hu et al. studied the effect of SA on hematological alterations in experimental lung cancer (Hu et al. 2021). Changes in the levels of hematological parameters such as leucocytes, neutrophils, lymphocytes, absolute lymphocyte count and absolute neutrophil count were observed in lung cancer-bearing animals. SA treatment effectively improved all the abnormalities in hematological parameters.

The level of immunoglobulin (IgG and IgM) production is diminished in patients with cancer, an indicative of compromised humoral immunity and immune reaction (Gasser et al. 2021). Modulation of immunoglobulin production during cancer can be considered as an alternate approach for the prevention of the disease. The effect of SA on modulating immunoglobulin levels in lung cancer in rats has been reported (Hu et al. 2021). SA administration markedly improved the levels of IgG and IgA in the treated animals compared to the untreated animals. It can be understood that SA has the capability to modulate immune response during cancer.

Effect of SA on inflammation

Chronic inflammation signifies an important pathologic basis for the majority of human cancers (Michels et al. 2021). There is copious evidence from animal and human studies that persistent inflammation works as a major driving force in the path to cancer (Blanchard and Girard 2021). It is reported that about 26% of all cancers are somehow related to chronic infection and inflammation and chronic inflammation is associated in all stages of carcinogenesis, i.e., initiation, promotion and progression (Missiroli et al. 2020). Even though inflammation functions as an adaptive host defense against infection or injury and is commonly a self-limiting process, abnormal regulation of inflammatory responses may result in several chronic ailments including cancer (Piotrowski et al. 2020). The regulatory role of SA on inflammation in B(a)P-induced lung cancer in Swiss albino mice was demonstrated (Hu et al. 2021). Lung cancer animals showed increase in the levels of pro inflammatory cytokines such as TNF-α (150 times) IL-6 (100 times) and IL-1β (140 times) suggesting inflammation. SA treatment was found to markedly reduce the levels of TNF-α, IL-6 and IL-1β levels. The anti-inflammatory effect of SA reported in this study is its ability to regulate NF-kB pathway. However, the exact molecular mechanism on which SA exerts its effect is not clear.

Effect of SA on cell cycle arrest

The cell cycle is central to keep continuity in cell proliferation and to ascertain the protection of proliferating cells from DNA damage. The key regulators of cell cycle are cyclin-dependent kinases (CDKs), cyclins, and CDK inhibitors (CKIs). Cancer development is often associated with loss/dysregulation of cell cycle (Feitelson et al. 2015). Many anticancer compounds are found to regulate cell cycle progression as a part of their chemopreventive/chemotherapeutic mechanism (Meeran and Katiyar 2008). Studies have reported that SA has the potential in arresting cancer cells at different phases of cell cycle progression through stimulation and inhibition of different protein regulators and checkpoints. For instance, Janakiraman et al. (2014) reported the effect of SA on cell cycle regulation in Hep-2, laryngeal carcinoma cell line. The findings of the study showed that SA induced an early G0/G1 phase arrest in Hep-2 cells in a dose-dependent manner. Zhao et al. (2021) found that SA induced G2/M phase cell cycle arrest in Hep G2 and SMMC-7721 cell lines. The percentage of apoptotic cells of HepG2 cells and SMMC-7721 cells in G2/M phase treatment increased from 12.79 ± 0.89% in control to 22.60 ± 2.26% and 26.00 ± 1.30% after SA along with cisplatin treatment. Similarly, Kampa et al. (2004) showed that SA significantly reduced the number of cells in the G2/M phase and enhanced the S phase in T47D breast cancer cells compared to the untreated cells.

Effect of SA on autophagy

Autophagy also known as type II programmed cell death plays a critical role in cancer. Autophagy has an active tumor-suppressive or tumor-stimulating function in various process and stages of cancer development (Bai et al. 2022). In the early stage of cancer, autophagy acts as a survival pathway and quality-control mechanism inhibits tumor initiation and suppresses cancer progression. During the later stages of tumor, autophagy functions as a dynamic degradation and recycling system, leading to the survival and growth of the tumors and induces aggressiveness of the cancers by helping in metastasis. This indicates that regulation of autophagy can be used as effective interventional strategies for cancer therapy (Russell and Guan 2022).

The autophagy inducing effect of SA has been reported by Zhao et al. (2021) in HepG2 and SMMC-7721 cells. MDC staining for autophagy showed increased number of green granular structures in cytoplasm and nucleus area of both SA along with cisplatin treated HepG2 and SMMC-7721 cells compared to the untreated cells. The protein expression of Beclin, Atg 5 increased and expression of p62 decreased in SA along with cisplatin treated HepG2 and SMMC-7721 cells. mRNA expressions of protein involved in autophagy, LC3-II also increased considerably in SA along with cisplatin treated HepG2 and SMMC-7721 cells.

Effect of SA on angiogenesis, cell invasion and metastasis

Angiogenesis is a complex physiological process through which the new blood vessels form from the existing vasculature. Angiogenesis plays a foremost function in the tumor growth and metastasis (Poto et al. 2022). Cancer cells are highly dependent on the vascularization for further growth of cells beyond 1–2 mm3 (Ozel et al. 2022). SA has been demonstrated to inhibit angiogenesis, cell invasion and metastasis in cancer cells through different mechanisms (Huang e t al. 2021; Eroglu et al. 2018).

Effect of SA on epithelial-to-mesenchymal transition (EMT)

Huang et al. (2021) reported the effect of SA on angiogenesis, cell invasion and metastasis in pancreatic cancer cell lines (PANC-1 and SW1990). SA (10 mM) treated cells showed decreased protein expression of EMT related proteins such as vimentin, MMP-9, MMP-2, and Snail and increased expression of E-cadherin in PANC-1 and SW1990 cell lines. Furthermore, with the increasing concentration of SA, the expression of MMP-9 and MMP-2 gradually decreased. This showed that SA can effectively regulate EMT.

Effect of SA on downregulation of AKT/Gsk-3β signal pathway

The AKT/Gsk-3β signal pathway regulates proliferation, invasion, apoptosis, and metabolism, and plays a prominent role in the progression of cancer. The regulatory role of SA on AKT/Gsk-3β signal pathway in prostate cancer cell lines has been reported (Huang et al. 2021). SA treatment downregulated phosphorylated AKT and Gsk-3β in PANC-1 and SW1990 prostate cancer cell lines. The results of the study showed that SA inhibited prostate cancer by the downregulation of AKT/ Gsk-3β signal pathway. Eroglu et al. (2018) have also reported the anticancer property of SA (1000 µM) on human prostate cancer cell lines (PC-3 and LNCaP) through a similar mechanism. Further experimentation in a wider range of cell lines is required to confirm the effect of SA.

Effect of SA on cell proliferation and apoptosis

Cell proliferation is thought to play an important role in several steps of the carcinogenic process. Apoptosis has now established its significance in various areas of biology, and it recently received outstanding attention as a vital area related to the development and treatment of cancer (Wong Kaewkhiaw 2022). Apoptosis is a distinct form of cell death explicated by characteristic morphological and biochemical features. Numerous studies have revealed that imbalance in the homeostatic mechanisms, which control cell proliferation and cell death (apoptosis), can add to the development and growth rate of a tumor (Shen et al. 2022). In fact, apoptosis has a central role in restricting the population expansion of tumor cells early in the process of carcinogenesis, and inhibition of apoptosis has been shown to play a significant part in the genesis of tumor (Kang et al. 2022). If DNA damaged cells no longer respond to apoptosis, mutations may be acquired and fixed through further proliferation, which may lead to malignant neoplasia. Therefore, it is important that apoptosis-inducing and proliferation-inhibiting activity may be considered as a primary aspect in determining the effectiveness of chemopreventive agents.

A number of studies have demonstrated that SA can inhibit cell proliferation in prostate cancer (Eroglu et al. 2017), liver cancer (Zhao et al. 2021), breast cancer (Raj Preeth et al. 2019), pancreatic cancer (Huang et al. 2021) and myeloid leukemia (Rajendran et al. 2017) and induce apoptosis in cell line models. Badr et al. (2019) studied the effect of free and nano-capsulated SA on human lung (A549) and colon cancer (Caco-2) cell lines. The protein expression of Bax and p53 was increased; Bcl-2 was decreased in SA (free and capsulated)-treated cells. Janakiraman et al. (2014) studied the apoptotic effect of SA on human laryngeal carcinoma cell line (HEp-2). SA-treated cells showed significant membrane blebbing, chromatic condensation, and innumerable micronuclei in cells indicating apoptosis. The apoptotic inducing effect of cisplatin combined with SA on the hepatic cancer cells (HCC) HepG2 and SMMC-7721 were investigated by Zhao et al. (2021). SA dose dependently induced apoptotis in both HepG2 and SMMC-7721 cell lines. It is reported that the percentage of apoptotic cells of HepG2 cells and SMMC-7721 cells in G2/M phase treatment increased from 12.79 ± 0.89% in control to 22.60 ± 2.26% and 26.00 ± 1.30% after SA along with cisplatin treatment. The apoptotic inducing function of SA on human hepatocellular carcinoma cell lines (Hep 3B and Hep G2) was studied (Eroglu et al. 2017). Results of qPCR analysis showed that the mRNA expressions of CASP3 and FAS were significantly increased to 23.37-fold and 27.47-fold in SA-treated Hep 3B cells. Similarly, the mRNA expression of CASP3 was increased to 1.53-fold; CASP8 to 1.77-fold; CASP9 to 1.21-fold; BAX to 1.47-fold and FAS to 1.39-fold. Other studies have also reported the apoptosis-inducing nature of SA in neuroblastoma (Tungalag and Yang 2021), breast cancer (Kampa et al. 2004) and oral cancer (Kalaimathi and Suresh 2015b).

Effect of SA as a co-adjuvant in anticancer therapy

SA acts in collaboration with other chemotherapeutic agents to improve treatment sensitivity. A study investigated the anticancer effects of cisplatin combined with SA against hepatic cancer cells (Zhao et al. 2021). SA in combination with cisplatin was found to effectively induce apoptosis, autophagy and prevented cell proliferation. This study showed that SA along with cisplatin treatment exhibited a better anti-tumorigenic effect compared to only cisplatin treatment in hepatocellular carcinoma.

Toxicity of SA

SA is found to be generally non-toxic, but few studies have reported its toxicity. One study reported that SA showed slightly increased cytotoxic activity than its ester derivate (Fan et al. 2009). The cytotoxic profiles of SA in V79 Chinese Hamster lung fibroblasts were reported. The study showed that SA up to 2000 µM concentration did not show any appreciable effects on the viability of V79 cells and at a very high concentration of above 5000 µM resulted in cytotoxic effects (Zheng et al. 2008). The genotoxic effect of SA on adenocarcinoma colon cells was reported by Lee-Manion et al. (2009). Results using Comet assay revealed that SA did not induce appreciable genotoxicity in human adenocarcinoma cells.

Future applications of SA

It is interesting to know that SA is principally involved in regulating oxidative stress, cellular antioxidants, cell proliferation, xenobiotic metabolism, metastasis, apoptosis, cell cycle, DNA damage, angiogenesis, inflammation and autophagy. Some studies on SA consistently explore that SA improves the effect of pro-apoptotic chemotherapeutic agents like cisplatin, especially in the human cell line models. In the future, further studies of SA are to be undertaken to explore its potential implication in treating different human carcinomas.


This review has summarized the plausible mechanisms involved in the anticancer effect of SA against different types of cancer in cell lines and animal models (Table 1; Fig. 2). Therefore, the bioavailability, toxicity and route of administration of SA requires further research and development. Moreover, since most of the investigations mentioned in the current work are based on in vitro studies, more findings on animal models and human subjects are highly recommended in the future in order to implement SA as a potential anticancer drug.

Table 1 Summary of the anticancer effects of Sinapic acid
Fig. 2
figure 2

Molecular targets of sinapic acid against cancer

Availability of data and materials

Not applicable.



Sinapic acid


Hepatic cancer cells




Carcinoembryonic antigen


Aryl hydrocarbon hydroxylase


Lactate dehydrogenase


Gamma glutamyl transpeptidase






DT diapharose


Superoxide dismutase




Glutathione reductase


Reduced glutathione


Lipid peroxidation


Reactive oxygen species


Dimethyl benza(a)nthracene


Tumor necrosis factor




Cyclin-dependent kinase


CDK inhibitors


Matrix metalloproteinase


Epithelial-to-mesenchymal transition


  • Alaofi AL (2020) Sinapic acid ameliorates the progression of streptozotocin (STZ)-induced diabetic nephropathy in rats via NRF2/HO-1 mediated pathways. Front Pharmacol 23(11):1119

    Article  Google Scholar 

  • Al-Ishaq RK, Overy AJ, Büsselberg D (2020) Phytochemicals and gastrointestinal cancer: cellular mechanisms and effects to change cancer progression. Biomolecules 10(1):105

    Article  CAS  PubMed Central  Google Scholar 

  • Anandakumar P, Jagan S, Kamaraj S, Ramakrishnan G, Titto AA, Devaki T (2008) Beneficial influence of capsaicin on lipid peroxidation, membrane-bound enzymes and glycoprotein profile during experimental lung carcinogenesis. J Pharm Pharmacol 60(6):803–808

    Article  CAS  PubMed  Google Scholar 

  • Ansari MA (2017) Sinapic acid modulates Nrf2/HO-1 signaling pathway in cisplatin-induced nephrotoxicity in rats. Biomed Pharmacother 93:646–653

    Article  CAS  PubMed  Google Scholar 

  • Badr DA, Amer ME, Abd-Elhay WM, Nasr MSM, Abhuamara MMT, Ali H et al (2019) Histopathological and genetic changes proved the anti-cancer potential of free and nano-capsulated sinapic acid. Appl Biol Chem 62:59

    Article  Google Scholar 

  • Bai Z, Peng Y, Ye X, Liu Z, Li Y, Ma L (2022) Autophagy and cancer treatment: four functional forms of autophagy and their therapeutic applications. J Zhejiang Univ Sci B 23(2):89–101

    Article  PubMed  PubMed Central  Google Scholar 

  • Balaji C, Muthukumaran J, Nalini N (2014) Chemopreventive effect of sinapic acid on 1,2-dimethylhydrazine-induced experimental rat colon carcinogenesis. Hum Exp Toxicol 33(12):1253–1268

    Article  CAS  PubMed  Google Scholar 

  • Balaji C, Muthukumaran J, Nalini N (2015) Effect of sinapic acid on 1,2 dimethylhydrazine induced aberrant crypt foci, biotransforming bacterial enzymes and circulatory oxidative stress status in experimental rat colon carcinogenesis. Bratisl Lek Listy 116(9):560–566

    CAS  PubMed  Google Scholar 

  • Bin Jardan YA, Ansari MA, Raish M, Alkharfy KM, Ahad A, Al-Jenoobi FI et al (2020) Sinapic acid ameliorates oxidative stress, inflammation, and apoptosis in acute doxorubicin-induced cardiotoxicity via the NF-κB-mediated pathway. Biomed Res Int 10:921796

    Google Scholar 

  • Blanchard L, Girard JP (2021) High endothelial venules (HEVs) in immunity, inflammation and cancer. Angiogenesis 24(4):719–753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bracci L, Fabbri A, Del Cornò M, Conti L (2021) Dietary polyphenols: promising adjuvants for colorectal cancer therapies. Cancers (basel) 13(18):4499

    Article  CAS  Google Scholar 

  • Bungau S, Abdel-Daim MM, Tit DM, Ghanem E, Sato S, Maruyama-Inoue M et al (2019) Health benefits of polyphenols and carotenoids in age-related eye diseases. Oxid Med Cell Longev 12(2019):9783429

    Google Scholar 

  • Cherng YG, Tsai CC, Chung HH, Lai YW, Kuo SC, Cheng JT (2013) Antihyperglycemic action of sinapic acid in diabetic rats. J Agric Food Chem 61(49):12053–12059

    Article  CAS  PubMed  Google Scholar 

  • de Lima Cherubim DJ, Buzanello Martins CV, Oliveira Fariña L, da Silva de Lucca RA (2020) Polyphenols as natural antioxidants in cosmetics applications. J Cosmet Dermatol 19(1):33–37

    Article  PubMed  Google Scholar 

  • Eroglu C, Kurar E, Avci E, Vural H (2017) Investigation of apoptotic effect of sinapic acid on Hep3B and HepG2 hepatocellular carcinoma cell lines. Proc 1:1000

    Google Scholar 

  • Eroğlu C, Avcı E, Vural H, Kurar E (2018) Anticancer mechanism of Sinapic acid in PC-3 and LNCaP human prostate cancer cell lines. Gene 10(671):127–134

    Article  Google Scholar 

  • Fan GJ, Jin XL, Qian YP, Wang Q, Yang RT, Dai F et al (2009) Hydroxycinnamic acids as DNA-cleaving agents in the presence of Cu(II) ions: mechanism, structure–activity relationship, and biological implications. Chemistry 15(46):12889–12899

    Article  CAS  PubMed  Google Scholar 

  • Feitelson MA, Arzumanyan A, Kulathinal RJ, Blain SW, Holcombe RF, Mahajna J et al (2015) Sustained proliferation in cancer: mechanisms and novel therapeutic targets. Semin Cancer Biol 35:S25-54

    Article  PubMed  PubMed Central  Google Scholar 

  • Fraga CG, Croft KD, Kennedy DO, Tomás-Barberán FA (2019) The effects of polyphenols and other bioactives on human health. Food Funct 10(2):514–528

    Article  CAS  PubMed  Google Scholar 

  • Gaspar A, Martins M, Silva P, Garrido EM, Garrido J, Firuzi O et al (2010) Dietary phenolic acids and derivatives. Evaluation of the antioxidant activity of sinapic acid and its alkyl esters. J Agric Food Chem 58(21):11273–11280

    Article  CAS  PubMed  Google Scholar 

  • Gasser M, Lissner R, Hsiao LL, Waaga-Gasser AM (2021) Abstract PO001: results from a preclinical study to evaluate the efficacy of polyvalent immunoglobulins on the imbalance of (anti-) inflammatory immune cell responses in clinical colorectal cancer. Cancer Immunol Res 2021:9

    Google Scholar 

  • Hausman DM (2019) What is cancer? Perspect Biol Med 62(4):778–784

    Article  PubMed  Google Scholar 

  • Hosny H, El Gohary N, Saad E, Handoussa H, El Nashar RM (2018) Isolation of sinapic acid from broccoli using molecularly imprinted polymers. J Sep Sci 41(5):1164–1172

    Article  CAS  PubMed  Google Scholar 

  • Hu X, Geetha RV, Surapaneni KM, Veeraraghavan VP, Chinnathambi A, Alahmadi TA et al (2021) Lung cancer induced by benzo(A)pyrene: Chemo protective effect of sinapic acid in swiss albino mice. Saudi J Biol Sci 28(12):7125–7133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang Z, Chen H, Tan P, Huang M, Shi H, Sun B et al (2021) Sinapic acid inhibits pancreatic cancer proliferation, migration, and invasion via downregulation of the AKT/Gsk-3β signal pathway. Drug Dev Res 3:721–724

    Google Scholar 

  • Iranda-Galvis M, Loveless R, Kowalski LP, Teng Y (2021) Impacts of environmental factors on head and neck cancer pathogenesis and progression. Cells 10(2):389

    Article  Google Scholar 

  • Jackson DN, Theiss AL (2020) Gut bacteria signaling to mitochondria in intestinal inflammation and cancer. Gut Microbes 11(3):285–304

    Article  PubMed  Google Scholar 

  • Janakiraman K, Suresh Kathiresan S, Mariadoss AV (2014) Influence of sinapic acid on induction of apoptosis in human laryngeal carcinoma cell line. Int J Modern Res Rev 2(5):165–170

    Google Scholar 

  • Kalaimathi J, Suresh K (2015a) Protective effect of sinapic acid against 7,12dimethyl benz(a)anthracene induced hamster buccal pouch carcinogenesis. Int J Curr Res Acad Rev 3:150–158

    CAS  Google Scholar 

  • Kalaimathi J, Suresh K (2015b) Sinapic acid attenuates 7,12 dimethyl benz(a)anthracene induced oral carcinogenesis by improving the apoptotic associated gene expression in hamsters. Asian J Pharmaceut Clin Res 8:6

    Google Scholar 

  • Kampa M, Alexaki VI, Notas G, Nifli AP, Nistikaki A, Hatzoglou A et al (2004) Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action. Breast Cancer Res 6(2):R63-74

    Article  CAS  PubMed  Google Scholar 

  • Kang YJ, Jang JY, Kwon YH, Lee JH, Lee S, Park Y et al (2022) MHY2245, a sirtuin inhibitor, induces cell cycle arrest and apoptosis in HCT116 human colorectal cancer cells. Int J Mol Sci 23(3):1590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee JY (2018) Anti-inflammatory effects of sinapic acid on 2,4,6-trinitrobenzenesulfonic acid-induced colitis in mice. Arch Pharm Res 41(2):243–250

    Article  CAS  PubMed  Google Scholar 

  • Lee HE, Kim DH, Park SJ, Kim JM, Lee YW, Jung JM et al (2012) Neuroprotective effect of sinapic acid in a mouse model of amyloid β(1–42) protein-induced Alzheimer’s disease. Pharmacol Biochem Behav 103(2):260–266

    Article  CAS  PubMed  Google Scholar 

  • Lee-Manion AM, Price RK, Strain JJ, Dimberg LH, Sunnerheim K, Welch RW (2009) In vitro antioxidant activity and antigenotoxic effects of avenanthramides and related compounds. J Agric Food Chem 57(22):10619–10624

    Article  CAS  PubMed  Google Scholar 

  • Mao QQ, Xu XY, Shang A, Gan RY, Wu DT, Atanasov AG, Li HB (2020) Phytochemicals for the prevention and treatment of gastric cancer: effects and mechanisms. Int J Mol Sci 21(2):570

    Article  CAS  PubMed Central  Google Scholar 

  • Marković JM, Petranović NA, Baranac JM (2005) The copigmentation effect of sinapic acid on malvin: a spectroscopic investigation on colour enhancement. J Photochem Photobiol B 78(3):223–228

    Article  PubMed  Google Scholar 

  • Martin-Cordero C, Jose Leon-Gonzalez A, Manuel Calderon-Montano J, Burgos-Moron E, Lopez-Lazaro M (2012) Pro-oxidant natural products as anticancer agents. Curr Drug Targets 13(8):1006–1028

    Article  CAS  PubMed  Google Scholar 

  • Meeran SM, Katiyar SK (2008) Cell cycle control as a basis for cancer chemoprevention through dietary agents. Front Biosci 1(13):2191

    Article  Google Scholar 

  • Michels N, van Aart C, Morisse J, Mullee A, Huybrechts I (2021) Chronic inflammation towards cancer incidence: a systematic review and meta-analysis of epidemiological studies. Crit Rev Oncol Hematol 1(157):103177

    Article  Google Scholar 

  • Missiroli S, Genovese I, Perrone M, Vezzani B, Vitto VA, Giorgi C (2020) The role of mitochondria in inflammation: from cancer to neurodegenerative disorders. J Clin Med 9(3):740

    Article  CAS  PubMed Central  Google Scholar 

  • Nićiforović N, Abramovič H (2014) Sinapic acid and its derivatives: natural sources and bioactivity. Comp Rev Food Sci Food Saf 13(1):34–51

    Article  Google Scholar 

  • Ozel I, Duerig I, Domnich M, Lang S, Pylaeva E, Jablonska J (2022) The good, the bad, and the ugly: neutrophils, angiogenesis, and cancer. Cancers 14(3):536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Piotrowski I, Kulcenty K, Suchorska W (2020) Interplay between inflammation and cancer. Rep Pract Oncol Radiother 25(3):422–427

    Article  PubMed  PubMed Central  Google Scholar 

  • Poto R, Cristinziano L, Modestino L, de Paulis A, Marone G, Loffredo S et al (2022) Neutrophil extracellular traps, angiogenesis and cancer. Biomedicines 10(2):431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raj Preeth D, Shairam M, Suganya N, Hootan R, Kartik R, Pierre K et al (2019) Green synthesis of copper oxide nanoparticles using sinapic acid: an underpinning step towards antiangiogenic therapy for breast cancer. J Biol Inorg Chem 24(5):633–645

    Article  CAS  PubMed  Google Scholar 

  • Rajendran N, Subramaniam S, Raja MRC, Brindha P, Kar Mahapatra S, Sivasubramanian A (2017) Plant phenyl-propanoids-conjugated silver nanoparticles from edible plant Suaeda maritima (L.) dumort. Inhibit proliferation of K562-human myeloid leukemia cells. Artif Cells Nanomed Biotechnol 45(7):1336–1342

    Article  CAS  PubMed  Google Scholar 

  • Roy SJ, Mainzen Prince PS (2013) Protective effects of sinapic acid on cardiac hypertrophy, dyslipidaemia and altered electrocardiogram in isoproterenol-induced myocardial infarcted rats. Eur J Pharmacol 699(1–3):213–218

    Article  CAS  PubMed  Google Scholar 

  • Russell RC, Guan KL (2022) The multifaceted role of autophagy in cancer. EMBO J 10:e110031

    Google Scholar 

  • Russell WR, Labat A, Scobbie L, Duncan GJ, Duthie GG (2009) Phenolic acid content of fruits commonly consumed and locally produced in Scotland. Food Chem 115:100–104

    Article  CAS  Google Scholar 

  • Scandolara TB, da Silva JC, Alves FM, Malanowski J, de Oliveira ST, Maito VT et al (2022) Clinical implications of lipid peroxides levels in plasma and tumor tissue in breast cancer patients. Prostaglandins Other Lipid Mediat 1(161):106639

    Article  Google Scholar 

  • Shah MA, Rogoff HA (2021) Implications of reactive oxygen species on cancer formation and its treatment. Semin Oncol 48(3):238–245

    Article  CAS  PubMed  Google Scholar 

  • Shen LW, Jiang XX, Li ZQ, Li J, Wang M, Jia GF et al (2022) Cepharanthine sensitizes human triple negative breast cancer cells to chemotherapeutic agent epirubicin via inducing cofilin oxidation-mediated mitochondrial fission and apoptosis. Acta Pharmacol Sin 43(1):177–193

    Article  CAS  PubMed  Google Scholar 

  • Shin DS, Kim KW, Chung HY, Yoon S, Moon JO (2013a) Effect of sinapic acid against carbon tetrachloride-induced acute hepatic injury in rats. Arch Pharm Res 36(5):626–633

    Article  CAS  PubMed  Google Scholar 

  • Shin DS, Kim KW, Chung HY, Yoon S, Moon JO (2013b) Effect of sinapic acid against dimethylnitrosamine-induced hepatic fibrosis in rats. Arch Pharm Res 36(5):608–618

    Article  CAS  PubMed  Google Scholar 

  • Shirley AM, Chapple C (2003) Biochemical characterization of sinapoylglucose:choline sinapoyltransferase, a serine carboxypeptidaselike protein that functions as an acyltransferase in plant secondary metabolism. J Biol Chem 278:19870–19877

    Article  CAS  PubMed  Google Scholar 

  • Tungalag T, Yang DK (2021) Sinapic acid protects SH-SY5Y human neuroblastoma cells against 6-hydroxydopamine-induced neurotoxicity. Biomedicines 9(3):295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Willenbrink TJ, Ruiz ES, Cornejo CM, Schmults CD, Arron ST, Jambusaria-Pahlajani A (2020) Field cancerization: definition, epidemiology, risk factors, and outcomes. J Am Acad Dermatol 83(3):709–717

    Article  CAS  PubMed  Google Scholar 

  • Wongkaewkhiaw S, Wongrakpanich A, Krobthong S, Saengsawang W, Chairoungdua A, Boonmuen N (2022) Induction of apoptosis in human colorectal cancer cells by nanovesicles from fingerroot (Boesenbergia rotunda (L.) Mansf.). PLoS ONE 17(4):e0266044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoon BH, Jung JW, Lee JJ, Cho YW, Jang CG, Jin C et al (2007) Anxiolytic-like effects of sinapic acid in mice. Life Sci 81(3):234–240

    Article  CAS  PubMed  Google Scholar 

  • Yoshida N, Horinouchi T, Eto K, Harada K, Sawayama H, Imamura Y et al (2022) Prognostic value of pretreatment red blood cell distribution width in patients with esophageal cancer who underwent esophagectomy: a retrospective study. Ann Surg Open 3(2):e153

    Article  Google Scholar 

  • Zhao J, Li H, Li W, Wang Z, Dong Z, Lan H et al (2021) Effects of sinapic acid combined with cisplatin on the apoptosis and autophagy of the hepatoma cells HepG2 and SMMC-7721. Evid Based Complet Alt Med 12:2021

    Google Scholar 

  • Zheng LF, Dai F, Zhou B, Yang L, Liu ZL (2008) Prooxidant activity of hydroxycinnamic acids on DNA damage in the presence of Cu(II) ions: mechanism and structure-activity relationship. Food Chem Toxicol 46(1):149–156

    Article  CAS  PubMed  Google Scholar 

Download references


Not applicable.


No funding was obtained for this study.

Author information

Authors and Affiliations



All authors have read and approved the manuscript. AP planned and written the manuscript, VMK helped in preparing the tables and figures. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Anandakumar Pandi.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

Authors declare that there are no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pandi, A., Kalappan, V.M. Mechanisms involved in the anticancer effects of sinapic acid. Bull Natl Res Cent 46, 259 (2022).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: