Curcumin, extracted from the root of turmeric, has been extensively studied for its anti-cancer properties with insights on cellular mechanisms of how it can help synergize with specific chemotherapy. Curcumin from turmeric enhanced the response of FOLFOX chemotherapy treatment in colorectal cancer patients as highlighted by a phase II clinical trial. However, cancer patients should take Curcumin supplements (concentrated curcumin extracted from turmeric) only under the guidance of the health practitioner as it may interact with other treatments such as Tamoxifen.
Turmeric is a spice that has been widely used for centuries in Asia not only as a key ingredient in Indian cuisine but in traditional Chinese medicine and Indian Ayurvedic medicine, to treat various health problems. More recently there has been extensive research on the anti-cancer properties of the key active ingredient Curcumin, present in turmeric (curcuma longa). Curcumin is extracted from the roots of Turmeric and it is characterized by a yellow orange pigment. There is an abundance of studies and observations published in thousands of peer reviewed journals on the therapeutic properties of Curcumin.
Curcumin from the Turmeric spice is a phytochemical with wide-ranging impact on many cellular processes, pathways, proteins and genes including different kinases, cytokines, enzymes and transcription factors. Thus Curcumin has many health-protective properties including antioxidant, anti-cancer, anti-inflammatory, antimicrobial, immunomodulatory, neuroprotective, and a broader protection to many organs and organ systems including the liver, kidney, skin etc. (Kocaadam B et al, Crit. Rev. Food Sci. Nutr., 2015)
In this blog we will summarize the experimental and clinical evidence for the chemopreventive and anticancer properties of Curcumin, the key active of the spice Turmeric. It is an easily accessible, low cost and low toxicity, natural phytochemical, chosen as one of the potential promising substances being tested in clinical trials by the US National Cancer Institute.
Despite the strong experimental and mechanistic evidence of Curcumin’s anticancer pharmacological potential, it has issues of poor absorption and low bioavailability in the body, in its natural form. This can be addressed through formulations that enhance its bioavailability. Additionally, through its interaction with drug metabolizing enzymes and drug transporters, it has high potential to interact with other drugs. Hence, there is a need for more well-designed clinical studies for defining the precise conditions and combinations in which Curcumin can be used. (Unlu A et al, JBUON, 2016)
Anti-Inflammatory Properties of Curcumin/Turmeric Provide Anti-Cancer Benefits
The key anti-cancer characteristics of Curcumin/Turmeric is due to its anti-inflammatory and immunomodulatory properties.
Cancer occurs when our cells are transformed due to mutations and defects caused by many different underlying causes including lifestyle, diet, stress, environment and underlying genetic factors. Our bodies are designed with guards and defense mechanisms at systemic and cellular levels. Our immune system is designed to identify anything that is foreign (a bacterial or viral infection) or anything within the body that is abnormal, and has processes and biological workflows to clear out the abnormality. Even at the cellular level as the cells divide for growth, renewal, wound healing and other routine body functioning, we have checks at every level starting with checking the accuracy of the master message in our genome, the DNA. There is an entire DNA damage sensing and repair machinery that is constantly at work for this process.
When cancer happens, the studies have confirmed that there is a defect at the cellular level with the DNA repair machinery causing more cellular damage and abnormality, and a systemic defect in the policing immune system that has overlooked and not been able to recognize and clear the abnormality. Hence the abnormal cells are allowed to survive and the rogue cells then take over the system and thrive and flourish as the disease progresses.
Inflammation is the process when the body inherently recognizes a defect or abnormality and recruits the body’s immune defenses to tackle the issue and clear out the problem. Mostly, all disorders including autoimmune disorders, degenerative disorders and even cancer are due to different dysfunctionalities of the immune system. In the case of cancer, the immune system is hijacked to not recognize but support the abnormal cells and aid in their growth.
There are many studies that have determined the cellular mechanisms for the anti-inflammatory actions of Curcumin extracted from Turmeric that provide the key anti-cancer benefit. Curcumin exerts its anti-inflammatory properties through interacting with several immune mediators such as inhibiting pro-inflammatory transcription factors such as Nuclear factor kappa B (NFKB), inhibits pro-inflammatory cytokines, chemokines, prostaglandins and even the reactive oxygen species (ROS). Many of these mediators are involved in multiple cell signaling pathways associated with cancer endpoints such as excessive cancer growth (proliferation), reduced cell death (apoptosis), excessive sprouting of new blood vessels (angiogenesis) and supporting the spread of the abnormal cancer cells to other parts of the body (metastasis). The immunomodulatory properties of Curcumin are not only due to inhibition of the cellular molecular targets but also it is able to effectively modulate the immune cells such as macrophages, dendritic cells, T-cells and B-lymphocytes, the body’s defense system. (Giordano A and Tommonaro G, Nutrients, 2019)
Experimental Studies on Anti-cancer Effects of Turmeric/Curcumin In Cancer
The anti-cancer effects of Curcumin/Turmeric have been investigated in many cancer cell lines and animal models. Curcumin has shown beneficial effects of reducing cancer cell growth in models of prostate cancer, breast cancer including triple negative breast cancer, esophageal and head and neck cancers, lung cancer and many others. (Unlu A et al, JBUON, 2016)
Additionally, there have been studies on assessing if Curcumin can enhance the sensitivity of chemotherapy drugs and radiation therapy.
- Curcumin was shown to increase the sensitivity of 5-fluorouracil in colorectal cancer cell lines. (Shakibaei M et al, PLoS One, 2014)
- Curcumin extracted from Turmeric experimentally enhanced the efficacy of cisplatin in head and neck and ovarian cancer cells. (Kumar B et al, PLoS One, 2014; Selvendiran K et al, Cancer Biol. Ther., 2011)
- Curcumin was reported to increase efficacy of paclitaxel in cervical cancer cells. (Sreekanth CN et al, Oncogene, 2011)
- In lymphoma, Curcumin was shown to enhance sensitivity to radiation therapy. (Qiao Q et al, Anticancer Drugs, 2012)
- In squamous cell lung cancer cells, Curcumin from Turmeric was reported to be synergistic with the chemotherapy drug vinorelbine. (Sen S et al, Biochem Biophys Res. Commun., 2005)
Clinical Studies on the Effect of Curcumin in Cancer
Curcumin is still being researched in many ongoing clinical studies, both as a monotherapy and in combination with other drugs.
- In a colorectal cancer clinical study, an oral formulation of curcumin was evaluated. There was an absence of toxicity with Curcumin, while 2 of the 15 patients showed stable disease after 2 months of Curcumin treatment. (Sharma RA et al, Clin Cancer Res., 2004) In another phase II study of 44 patients with colon cancer lesions, use of Curcumin for 30 days was reported to reduce the number of lesions by 40%. (Carroll RE et al, Cancer Prev. Res. (Phila), 2011)
- In a phase II trial of a Curcumin oral formulation in 25 advanced pancreatic cancer patients, two patients showed clinical biological activity with one patient reported to have stable disease for >18 months and another having a brief but significant tumor regression. (Dhillon N et al, Clin Cancer Res., 2008)
- A clinical study in chronic myeloid leukemia (CML) patients, therapeutic effect of the combination of Curcumin along with Imatinib (the standard of care drug for CML) was evaluated. The combination showed better efficacy than Imatinib alone. (Ghalaut VS et al, J Oncol. Pharm Pract., 2012)
- In breast cancer patients, Curcumin is under investigation in monotherapy (NCT03980509) and in combination with paclitaxel (NCT03072992). It is also being evaluated in other clinical studies for low-risk prostate cancer, cervical cancer, endometrial cancer, uterine sarcoma and others. (Giordano A and Tommonaro G, Nutrients, 2019)
- A recent phase II clinical study in patients with metastatic colorectal cancer (NCT01490996) compared the overall survival of patients receiving the combination chemotherapy FOLFOX (folinic acid/5-fluorouracil/oxaliplatin treatment) with and without Curcumin supplements (from Turmeric). Addition of Curcumin to FOLFOX was found to be safe and tolerable for colorectal cancer patients and did not exacerbate the side-effects of the chemo. In terms of response rates, the Curcumin + FOLFOX group had a much better survival outcome with progression free survival being 120 days longer than FOLFOX group and overall survival being more than doubled. (Howells LM et al, J Nutr, 2019) Including Curcumin as part of the colorectal cancer patients’ diet when taking FOLFOX chemotherapy may be beneficial.
Interaction of Curcumin with Other Drugs
Curcumin, though recognized as a generally safe ingredient by the FDA (Food and Drug Administration), has evidence that it affects the drug metabolizing cytochrome P450 enzymes. Therefore, it has the potential to interact with some drugs and interfere with the drug efficacy. There are studies on its interactions with drugs including antiplatelet drugs, and other cancer and chemotherapy drugs including Tamoxifen, doxorubicin, cyclophosphamide, tacrolimus and others. (Unlu A et al, JBUON, 2016)
Curcumin’s antiplatelet property can increase the risk of bleeding when used with anticoagulants. Its antioxidant property can interfere with the mechanism of action of chemotherapy drugs such as cyclophosphamide and doxorubicin. (Yeung KS et al, Oncology J, Integrative Oncol., 2018)
Curcumin from Turmeric interacts with Tamoxifen treatment, the Standard of Care for Hormone Positive Breast Cancer
The oral drug Tamoxifen is metabolized in the body into its pharmacologically active metabolites through the cytochrome P450 enzymes in the liver. Endoxifen is the clinically active metabolite of Tamoxifen, that is the key mediator of efficacy of tamoxifen therapy (Del Re M et al, Pharmacol Res., 2016). Some earlier studies done on rats had shown that there is a drug-drug interaction between Curcumin and Tamoxifen. Curcumin inhibited the cytochrome P450 mediated metabolism of tamoxifen’s conversion to its active form (Cho YA et al, Pharmazie, 2012). A recently published prospective clinical study (EudraCT 2016-004008-71/NTR6149) from the Erasmus MC Cancer Institute in the Netherlands, tested this interaction between Curcumin from Turmeric (with or without piperine) and Tamoxifen treatment in breast cancer patients (Hussaarts KGAM et al, Cancers (Basel), 2019). The researchers assessed the levels of Tamoxifen and Endoxifen in presence of Curcumin.
The results showed that the concentration of the active metabolite Endoxifen decreased with Curcumin. This decrease in Endoxifen was statistically significant. Therefore, if Curcumin supplement (from Turmeric) is taken along with Tamoxifen treatment for breast cancer, it can lower the concentration of the active drug below its threshold for efficacy and potentially interfere with the therapeutic impact of the drug.
Turmeric, the orange-yellow spice, has been in use for centuries, even before its active ingredient Curcumin was identified, for its many health benefits. It is used as an anti-inflammatory and even applied directly on wounds to enhance wound healing. A pinch of turmeric with hot milk has been an age old antibacterial and immune boosting remedy used in households today, as per traditional wisdom. It is an ingredient of curry powder and is commonly and extensively used as part of Indian and Asian cuisines. A spoonful of raw and grated turmeric root along with black pepper and lemon is another common combination used on a routine basis for its anti-diabetic, anti-arthritic, immune boosting effect. Hence as a natural food and spice, turmeric is widely and extensively consumed.
Today, there are all kinds of turmeric and Curcumin extracts, tablets, capsules, and various formulations sold in the market, riding on the well known health benefits. However, Curcumin is known to have poor absorption and bioavailability in the body. When present in combination with black pepper or piperine or bioperine, it has improved bioavailability. Curcumin products are classified as herbals and botanicals that are not strictly regulated like drugs. Therefore, despite the abundance of Curcumin products in the market, one needs to be aware of selecting the product with the right formulation and supplement qualification labels from USP, NSF etc, to assure a better quality of the product.
As detailed in the blog, there are lot of experimental studies in many different cancer cells and animal models that show how Curcumin is not only able to inhibit cancer growth and other cancer endpoints, but have also mechanistically teased out the biological rationales for the way Curcumin is working in providing anti-cancer benefits. There are some clinical studies that have shown a modest benefit and have shown improvement in drug efficacy of certain cancer treatments including chemotherapy and radiation treatment, in combination with Curcumin (from Turmeric).
However, unlike the stringent requirements for clinical drug studies, the use of Curcumin formulations and concentrations have not been consistent and standardized across the many clinical studies. Additionally, due to the known low bioavailability issue of natural Curcumin, the results in clinical studies have not been very impressive and convincing. Moreover there are data on interaction of Curcumin with other treatments that could impact the efficacy of the drug. Hence for all the above reasons, besides using turmeric in our food and diet and maybe a qualified curcumin formulation for its immune boosting properties, the use of Curcumin by cancer patients is not recommended unless under the guidance of the health practitioner.
Cancer patients often have to deal with different chemotherapy side effects which affect their quality of life and look out for alternative therapies for cancer.Taking the right nutrition and supplements based on scientific considerations (avoiding guesswork and random selection) is the best natural remedy for cancer and treatment related side-effects.