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Curcumin as Chemopreventive Agent and Chemosensitizer

Curcumin as Chemopreventive Agent and Chemosensitizer

Broader research has led to the development of varied mono targeted therapies for managing the effects of cancer on the population. The death rate persists due to the increasing rate of cancer development. The development of chemoresistance is due to the modulation of several genes, proteins, and pathways. Hence, there is a need for safe and multitargeted agents to inhibit chemoresistance and, in turn, sensitize the cancer cells to chemotherapeutic agents. Several natural compounds have been identified to possess chemopreventive and chemosensitive features and among all is Curcumin which shows significant efficacy in cancer treatment. Curcumin has been used in traditional medicine in Asia, conducting antioxidant, antibacterial, antiviral, antifungal, anti-inflammatory, and hepatoprotective activities. It acts as a chemopreventive agent by inducing apoptosis and arrest of the cell cycle in different cancer cells by affecting the molecular targets like upregulation of Cdk inhibitors and p53 and downregulation of cyclin D1, Cdk-1, CDC-2, and NF-kB (Aggarwal & Shishodia, 2006).

Curcumin exhibits modulation of multiple targets by regulating transcription factors, inflammatory cytokines, growth factors, different protein kinases, and various other enzymes. Safety and tolerability have been obtained by conducting further clinical trials while providing cost-effectiveness and advantages by using Curcumin. Also, Curcumin has shown efficacy in modulating different cell signalling pathways and various signalling biomolecules; Curcumin serves as an effective chemosensitizer for other chemotherapeutic agents such as 5-FU, doxorubicin, paclitaxel, cisplatin, and celecoxib in different malignancies. 

Curcumin efficacy as a chemopreventive agent and chemosensitizer

Curcumin possesses the natural potential for preventing side effects caused by chemotherapy during cancer treatment. Chemotherapy is known as the most common therapeutic modality in treating cancer. The drugs used in chemotherapy show limited access with significant side effects involving myelosuppression, gastrointestinal toxicity, cardiotoxicity, hepatotoxicity, neurotoxicity, ototoxicity, etc. These side effects further make the patients discontinue their chemotherapy treatment (Irving et al., 2015).

Most chemotherapy drugs are challenged by drug resistance and drug-induced toxicity. A combination of therapy is recommended for avoiding drug resistance and reducing toxicity evolved from the drug. Therefore, enhancing clinical cancer treatment by combining medicine is considered an essential approach in chemotherapy. The food-derivative natural compound such as Curcumin has shown anticancer activities and is regarded as a better agent for combination therapy with existing chemotherapeutic drugs. Curcumin shows anticancer activities involving the inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). The combinational therapy treatment of using Curcumin with other chemotherapeutic drugs such as cisplatin, doxorubicin, 5-fluorouracil, and gemcitabine enhanced the therapeutic efficacy. NF-κB is a major downstream effector that showed chemoresistance of many medicinal drugs. Also, the downregulation of NF-κB by Curcumin leads to efficacy in sensitizing chemotherapeutic drugs and thus increasing therapeutic effectiveness. Therefore, combining Curcumin with other anticancer available medicines has improved the effects of chemotherapy.

Curcumin is used as adjuvant therapy showing effectiveness in preventing the side effects of chemotherapy. Curcumin prevents carcinogenesis and enhances the clinical efficacy of chemotherapy through sensitizing cancer cells to the commonly integrated chemotherapy while protecting the normal cells from chemotherapy-induced damages. It can reduce chemotherapy-induced toxicity by removing intracellular ROS in normal tissues and modulating a series of target molecules, including adhesion molecules, inflammatory factors, transcription and growth factors, apoptosis-related proteins, some enzymes and kinases, etc. (Benzer et al., 2018). 

References

  1. Bordoloi, D., K Roy, N., Monisha, J., Padmavathi, G., & B Kunnumakkara, A. (2016). Multi-targeted agents in cancer cell chemosensitization: What we learnt from curcumin thus far. Recent patents on anti-cancer drug discovery, 11(1), 67-97. 
  2. Aggarwal, B. B., & Shishodia, S. (2006). Molecular targets of dietary agents for prevention and therapy of cancer. Biochemical pharmacology, 71(10), 1397-1421. https://doi.org/10.1016/j.bcp.2006.02.009
  3. Irving, G. R., Iwuji, C. O., Morgan, B., Berry, D. P., Steward, W. P., Thomas, A., … & Howells, L. M. (2015). Combining curcumin (C3-complex, Sabinsa) with standard care FOLFOX chemotherapy in patients with inoperable colorectal cancer (CUFOX): study protocol for a randomised control trial. Trials, 16(1), 1-10. doi: 10.1186/s13063-015-0641-1

Benzer, F., Kandemir, F. M., Ozkaraca, M., Kucukler, S., & Caglayan, C. (2018). Curcumin ameliorates doxorubicin‐induced cardiotoxicity by abrogation of inflammation, apoptosis, oxidative DNA damage, and protein oxidation in rats. Journal of Biochemical and Molecular Toxicology, 32(2), e22030. doi: 10.1002/jbt.22030

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