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  • Writer's pictureJourdan Delacruz

Effects of Curcumin on Cancer Prevention and Treatment

Specific Topic: Mechanisms of Action

Thesis: Curcumin exhibits anticancer properties that may enhance cancer therapy and help prevent the onset of various cancers.

Jourdan Delacruz, The University of Northern Colorado

FND 451 Advanced Nutrition




In recent years, curcumin has gained attention from researchers, clinicians, and the general public for its anti-cancer properties. The perceived benefits to human health encompass cancer prevention and treatment through various mechanisms. Curcumin acts as a modulator of several molecular pathways involved in tumorigenesis, cell proliferation, and the expression of specific genetic markers. Specifically, the suppression of tumor genes, the induction of apoptosis, and the inhibition of tumor formation result in the reduction of cancer development.


Curcumin is involved in a variety of cellular mechanisms that are significant to cancer prevention. The suppression of tumor genes plays a critical role in the inhibition of oncogenesis. Normally, tumor suppressor genes regulate cell division but when there is a mutation to these genes, this function is reduced, and uncontrollable cell growth occurs. The TP53 gene that encodes p53 tumor suppressor protein is inherently responsible for regulating many molecular pathways, including apoptosis (death) of cancer cells. A mutation in p53 can result in a cascade effect of uncontrolled transactivation of these cells (Keyvani‐Ghamsari, Khorsandi, & Gul, 2020). This mutation is found in a range of 10-100% of all human cancer patients and leads to increased chemotherapy resistance (Keyvani‐Ghamsari et al., 2020). One study suggests that curcumin may induce apoptosis and autophagy (breakdown) by activating p53 gene pathways and, simultaneously, inhibiting PI3K gene pathways of gastric cells (Fu, Wang, C., Yang, Wei, Xu, Hu, Zhang, Wang, W., Yan, & Cai, 2018).


The induction of apoptosis of cancer cells is another mechanism in which curcumin prevents the development of various cancers. Apoptosis is a normal cellular function in which programmed cell death occurs in order to eliminate unwanted cells and is regulated by encoded apoptotic genes and proteins. Curcumin is responsible for the upregulation of pro-apoptotic genes while simultaneously downregulating anti-apoptotic genes; as well as, the induction of apoptotic proteins: Bax and bcl-2 (Singh, Barnes, D'Souza, & Mishra, 2021). The Bcl-2 family of proteins is involved in a series of apoptotic, intrinsic pathways and may be a “...promising target for altering tumor cell sensitivity” (Singh et al., 2021). Curcumin modulates these Bcl-2 pathways to induce apoptosis of certain cancer cells. Additionally, in the Fu et al., (2018) study mentioned earlier, the relationship between curcumin treatment concentration and the rate of apoptosis of gastric cells was further explored. The results showed the rate of apoptosis enhanced with the increase in curcumin concentration, suggesting gastric cell apoptosis may be dose-dependent.


Similarly, curcumin can suppress tumor progression by inactivation of vascular endothelial growth factor (VEGF). VEGF is an important angiogenic factor that is responsible for the growth of new blood vessels from pre-existing blood vessels. VEGF promotes tumor angiogenesis and induces anti-apoptotic proteins within endothelial cells (Basak, Srinivas, Mallepogu, & Duttaroy, 2020). Basak et al., (2020) found curcumin to inhibit VEGF function and VEGF receptors, including protein expression of pro-angiogenic factor VEGF receptor-2 and fatty acid-binding protein-4 (FABP4). Curcumin inhibits this pathway and the activation of subsequent pathways that ensure the survival and promotion of tumor cells. The suppression of critical cell signaling pathways induced by curcumin has shown to be a beneficial preventative measure to the development of certain cancers.


The mechanisms of curcumin used in cancer treatment are very similar to those used in cancer prevention. The induction of apoptosis and the suppression of tumor proliferation are key mechanisms used in clinical and research settings as complementary strategies to cancer therapies. These mechanisms help slow the progression of existing cancers and tumor formation. Yang, Huang, Zhou, Xiong, Zhao, Fang, Zhang, Li, & Zhu (2022) found apoptotic ratios of MDA-MB-231 and MDA-MB-469 cells in breast cancer were significantly increased when breast cancer treatment was combined with curcumin treatment due to reduced levels of B-cell lymphoma-2 induced by curcumin. Additional studies have been conducted and found curcumin’s apoptotic properties useful in the treatment of prostate, tongue, and cervical cancer (Yang et al., 2022). Another essential anticancer mechanism includes the inhibition of carcinogenic cell migration and invasion. Yang et al., (2022) utilized wound healing assays to track the spread of MCF-7 breast cancer cells. The results indicated a significant reduction in the invasion and migration of these cells. Additionally, curcumin has been shown to reduce the proliferation of cells as evidenced by the reduction in tumor weight, size, and volume found in non-human trials. The reason behind these findings is an interruption in the normal cell cycle. As noted earlier, curcumin is responsible for triggering G2/M arrest in breast cancer MCF-7, MDA-MB-453, and MDA-MB-231 cells which disrupts the proliferation of these cells (Yang et al., 2022).


The information collected from in-vitro and in vivo studies on curcumin’s antiproliferative, antiangiogenic, and apoptotic properties has encouraged medicine to adopt curcumin treatment as an adjuvant therapy strategy. It has been found that curcumin maximizes the effectiveness of cancer therapy and may improve drug delivery (Bashang & Tamma, 2019). Anticancer properties of curcumin work alongside anti-cancer drugs to reduce the growth and spread of cancer cells. Curcumin appears to have high selectivity to cancer cells specifically due to its effect on the Nrf2 transcription factor. Curcumin will activate Nrf2 which is responsible for tight regulation of the cell life cycle, apoptosis, and cell signaling (Bashang & Tamma, 2019). Additionally, curcumin modulates certain genes, such as cyclin-dependent kinase inhibitor 1A, which are also responsible for cell apoptosis and arrest (Bashang & Tamma, 2019). These cell-targeting mechanisms are extremely applicable to cancer treatment and have shown to be effective in liver, pancreatic, and colorectal cancers. Additionally, drug delivery has been shown to be positively affected by curcumin treatment in vitro. In one study, whole turmeric extract treatment was used on rats and followed by methotrexate, a common chemotherapy drug. The results showed increased “upregulation of cellular antioxidants, lowered serum liver biochemical markers, and lowered lipid peroxidation” (Bashang & Tamma, 2019). These findings may suggest improved effectiveness of drug delivery, however, more research in human trials is needed.


Lastly, the possibility of alleviating the negative side effects of cancer treatment through the use of curcumin treatment has also been explored. In Wang, Gao, Xu, Liu, Tian, Liu, & Zhou (2022), patients with ovarian cancer and on PARP inhibitor (PARPi) therapy were examined to see if an array of phytochemicals, including curcumin, would alleviate side effects associated with this type of treatment. Mutations in the BRCA gene (common in ovarian cancers) reduce cellular antioxidant capacity resulting in “...cardiovascular endothelial damage and atherosclerosis” (Wang et al., 2022). PARPi has been shown to exhibit hematologic toxicity resulting in “...thrombocytopenia, fatigue, nausea, and vomiting” (Wang et al., 2022). These associated side effects of chemotherapy greatly impact a patient’s quality of life. Wang et al., (2022) found curcumin to reduce common side effects of PARPi treatment, including nausea and vomiting, via positively influencing gastrointestinal motility and gastric emptying. 80% of patients also reported reduced general fatigue (Wang et al., 2022). When treating ovarian cancer patients, curcumin is being considered as an adjuvant therapy option to alleviate the risk of cardiovascular disease and PARPi side effects that BRCA mutations can cause.


The mechanisms of curcumin’s anti-cancer properties suggest beneficial applications to cancer prevention and treatment amongst a variety of different cancers. Studies are further being conducted in vivo as the prospects of the current literature are looking promising for human health and the future of medicine.



References:

Basak, S., Srinivas, V., Mallepogu, A., & Duttaroy, A. K. (2020). Curcumin stimulates angiogenesis through VEGF and expression of HLA‐G in first‐trimester human placental trophoblasts. Cell Biology International, 44(5), 1237–1251. https://doi.org/10.1002/cbin.11324

Bashang, H., & Tamma, S. (2019). The use of curcumin as an effective adjuvant to cancer therapy: A short review. Biotechnology and Applied Biochemistry, 67(2), 171–179. https://doi.org/10.1002/bab.1836

Fu, H., Wang, C., Yang, D., Wei, Z., Xu, J., Hu, Z., Zhang, Y., Wang, W., Yan, R., & Cai, Q. (2018). Curcumin regulates proliferation, autophagy, and apoptosis in gastric cancer cells by affecting PI3K and p53 signaling. Journal of Cellular Physiology, 233(6), 4634–4642. https://doi.org/10.1002/jcp.26190

Keyvani‐Ghamsari, S., Khorsandi, K., & Gul, A. (2020). Curcumin effect on cancer cells' multidrug resistance: An update. Phytotherapy Research, 34(10), 2534–2556. https://doi.org/10.1002/ptr.6703

Singh, S., Barnes, C. A., D'Souza, J. S., Hosur, R. V., & Mishra, P. (2021). Curcumin, a potential initiator of apoptosis via direct interactions with bcl‐xl and bid. Proteins: Structure, Function, and Bioinformatics, 90(2), 455–464. https://doi.org/10.1002/prot.26238

Wang, C., Gao, P., Xu, J., Liu, S., Tian, W., Liu, J., & Zhou, L. (2022). Natural phytochemicals prevent side effects in BRCA-mutated ovarian cancer and PARP inhibitor treatment. Frontiers in Pharmacology, 13. https://doi.org/10.3389/fphar.2022.1078303

Yang, Z.-J., Huang, S.-Y., Zhou, D.-D., Xiong, R.-G., Zhao, C.-N., Fang, A.-P., Zhang, Y.-J., Li, H.-B., & Zhu, H.-L. (2022). Effects and mechanisms of curcumin for the Prevention and management of cancers: An updated review. Antioxidants, 11(8), 1481. https://doi.org/10.3390/antiox11081481

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