Introduction
Curcumin, a biologically active polyphenolic compound found in turmeric, has been consumed in Asia for centuries for its medicinal properties. It is a potent antioxidant, anti-inflammatory, and antimicrobial agent that has been researched for its potential to prevent and treat various diseases, including cancer [1]. Long valued in naturopathic medicine, curcumin is most often prescribed to help control inflammation in chronic disease. More recently, there has been growing interest in its potential role as an adjunct therapy during chemotherapy. This short article will review some of the evidence surrounding the use of curcumin as an adjunctive treatment during chemotherapy, exploring both supportive and conflicting studies.
Mechanism of Action
Curcumin's potential as a therapeutic agent in chemotherapy lies in its multifaceted mechanisms of action. It is an anti-proliferative agent that induces apoptosis (programmed cell death) in a variety of cancer cell lines, including breast, colorectal, pancreatic, and prostate cancer [2]. Curcumin also interferes with the inflammatory pathways that are often upregulated in cancer [3]. Moreover, it has been shown to inhibit angiogenesis (formation of new blood vessels) and metastasis (spread of cancer) [4].
Curcumin as a Chemotherapeutic Adjuvant: Supportive Studies
Many studies support the use of curcumin as an adjuvant during chemotherapy.
A study by Bayet-Robert et al. [5] on 14 metastatic breast cancer patients found that a combination of curcumin and docetaxel, a chemotherapy drug, reduced the size of the tumor and the levels of circulating cancer markers. There was also a decrease in adverse events.
In another study involving 40 colorectal cancer patients, James et al. [6] discovered that a combination of curcumin and FOLFOX chemotherapy (5-fluorouracil, leucovorin, and oxaliplatin) improved the response rate and overall survival compared to FOLFOX chemotherapy alone.
Preclinical research has shown that curcumin can potentiate the effects of chemotherapeutic agents and reduce their side effects. Bayet-Robert et al. [7] showed that curcumin enhances the efficacy of cisplatin in ovarian cancer cells and reduces nephrotoxicity, a common side effect of this drug.
Curcumin has also been shown to overcome drug resistance, a significant challenge in cancer chemotherapy. A study by Lin et al. [8] demonstrated that curcumin could resensitize drug-resistant pancreatic cancer cells to gemcitabine, a chemotherapeutic agent.
Conflicting Studies
While a considerable amount of research supports the use of curcumin as an adjuvant during chemotherapy, some studies suggest otherwise.
A study by Kanai et al. [9] in patients with pancreatic cancer showed no significant improvement in overall survival or progression-free survival when curcumin was added to gemcitabine treatment. The authors suggested that the poor absorption of curcumin might have contributed to the lack of effect.
Another study by Epelbaum et al. [10] involving lung cancer patients found no significant difference in survival rates between patients receiving curcumin and chemotherapy and those receiving chemotherapy alone. They proposed that the high dose of curcumin used might have interfered with the chemotherapeutic agent's effectiveness.
Additionally, curcumin has been found to interact with certain drugs, potentially reducing their efficacy. Steward et al. [11] found that curcumin could reduce the bioavailability of irinotecan, a chemotherapeutic agent, possibly compromising its anti-cancer effect.
Bioavailability of Curcumin
One of the major challenges in the therapeutic use of curcumin is its poor
bioavailability, largely due to poor absorption, rapid metabolism, and rapid systemic elimination [12]. This can limit its effectiveness as an adjunct to chemotherapy.
However, several strategies are being explored to improve curcumin's bioavailability. This includes the use of adjuvants like piperine, which inhibits the metabolism of curcumin, thus increasing its bioavailability [13]. Furthermore, the use of nanotechnology in creating nano-curcumin formulations has shown promising results in improving its absorption [14].
Conclusion
The potential benefits of curcumin as an adjunct therapy during chemotherapy are promising, with numerous studies suggesting that it can enhance the efficacy of chemotherapy, reduce side effects, and overcome drug resistance. However, conflicting studies underscore the need for further research to validate these findings and determine the optimal dosing and delivery methods for curcumin. The issue of curcumin's poor bioavailability is an important factor to consider and is currently being addressed through various strategies. There is no question that further large-scale, randomized controlled trials are needed to definitively establish the role of curcumin in cancer chemotherapy. From a metabolic perspective however, curcumin if prescribed properly, provides too much potential benefit to not be considered -especially in the context of escalating inflammation, as seen in progressive metastatic disease.
References
Prasad S, Aggarwal BB. Turmeric, the Golden Spice: From Traditional Medicine to Modern Medicine. In: Benzie IFF, Wachtel-Galor S, editors. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. Boca Raton (FL): CRC Press/Taylor & Francis; 2011.
Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB. Curcumin and cancer: An "old-age" disease with an "age-old" solution. Cancer Lett. 2008;267(1):133-64.
Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 2003;23(1A):363-98.
Kunnumakkara AB, Anand P, Aggarwal BB. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett. 2008;269(2):199-225.
Bayet-Robert M, Kwiatkowski F, Leheurteur M, et al. Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer. Cancer Biol Ther. 2010;9(1):8-14.
James MI, Iwuji C, Irving G, et al. Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy. Cancer Lett. 2015;364(2):135-41.
Bayet-Robert M, Morvan D. Metabolomics reveals metabolic targets and biphasic responses in breast cancer cells treated by curcumin alone and in association with docetaxel. PLoS One. 2013;8(3):e57971.
Lin YG, Kunnumakkara AB, Nair A, et al. Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-kappaB pathway. Clin Cancer Res. 2007;13(11):3423-30.
Kanai M, Yoshimura K, Asada M, et al. A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer. Cancer Chemother Pharmacol. 2011;68(1):157-64.
Epelbaum R, Schaffer M, Vizel B, Badmaev V, Bar-Sela G. Curcumin and gemcitabine in patients with advanced pancreatic cancer. Nutr Cancer. 2010;62(8):1137-41.
Steward WP, Gescher AJ. Curcumin in cancer management: recent results of analogue design and clinical studies and desirable future research. Mol Nutr Food Res. 2008;52(9):1005-9.
Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007;4(6):807-18.
Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998;64(4):353-6.
Yallapu MM, Nagesh PKB, Jaggi M, Chauhan SC. Therapeutic Applications of Curcumin Nanoformulations. AAPS J. 2015;17(6):1341-1356.