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. Researchers have identified several natural compounds to possess chemopreventive and chemosensitive features and among all is Curcumin which shows significant efficacy in cancer treatment.
Experts have used curcumin 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 1. 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; it 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 chemo preventive agent and chemosensitizer
It possesses the natural potential for preventing side effects caused by chemotherapy during cancer treatment. Chemotherapy is 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 2.
Most chemotherapy drugs are challenged by drug resistance and drug-induced toxicity. Doctors recommend a combination of therapy for avoiding drug resistance and reducing toxicity evolved from the drug. Therefore, enhancing clinical cancer treatment by combining medicine is 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. 3.
- 1.Aggarwal BB, Shishodia S. Molecular targets of dietary agents for prevention and therapy of cancer. Biochemical Pharmacology. Published online May 2006:1397-1421. doi:10.1016/j.bcp.2006.02.009
- 2.Irving GR, Iwuji CO, Morgan B, et al. 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. Published online March 24, 2015. doi:10.1186/s13063-015-0641-1
- 3.Benzer F, Kandemir FM, Ozkaraca M, Kucukler S, Caglayan C. Curcumin ameliorates doxorubicin-induced cardiotoxicity by abrogation of inflammation, apoptosis, oxidative DNA damage, and protein oxidation in rats. J Biochem Mol Toxicol. Published online January 5, 2018:e22030. doi:10.1002/jbt.22030