How Curcumin Targets CancerSeptember 2016
By Virginia Chen
One in four Americans will die from cancer.1
Despite clinical successes using new immunotherapy drugs, cancer is still killing over 560,000 Americans each year.
Conventional medicine recognizes prevention as an essential element in today’s “War on Cancer.”
Curcumin is a natural compound extracted from the spice turmeric. An accumulation of evidence indicates its cancer-preventive effects, leading one scientist to call curcumin:
“An ideal chemopreventive agent with its low toxicity, affordability, and easy accessibility.”2
Curcumin has emerged in this role after 30 years of research at the National Cancer Institute, which has been testing various substances for their potential preventive effects.2
According to the National Cancer Institute, after testing more than 1,000 candidates, just 40 indicated promise. Curcumin is one of the leading members of that elite group.
Curcumin has reached the stage of clinical trials, although it has been in use since ancient times as a remedy for many illnesses in different cultures.2
Used alone or in combination with other therapies, curcumin has an impressive track record in prevention and treatment.3
Here is a brief review of the research indicating the benefit of curcumin in the prevention of common malignancies, its potential to help treat certain cancers and to minimize the side effects associated with radiation and chemotherapy.
Curcumin’s Unparalleled Cancer-Fighting Abilities
For those who have been diagnosed with cancer, it can seem as though the cancer developed practically overnight. In reality, the development of cancer is a lengthy process that may take years or even decades to play out.
The initiation and progression of a cell into a malignancy involves multiple steps. At each step there is a disruption in at least one pathway that controls normal cellular processes.3
The good news about this complex process is that it represents a potential point of intervention to delay or prevent a malignancy from forming.2,3
Curcumin has now been shown to have an impact on virtually all of the major targets involved in the cancer development process. These effects give curcumin potent preventive and therapeutic properties against many different kinds of cancer.3
In general, chemopreventive substances (those used to inhibit, delay, or reverse cancer development) are grouped by their general mechanism: those that slow the proliferation of cancer cells, those that reduce oxidative stress, and those that block carcinogens from forming. Curcumin is a member of all three groups, giving it unparalleled cancer-fighting abilities.2
Curcumin’s Multiple Mechanisms of Action
Curcumin’s actions involve various combinations of mechanisms, including:2
- Survival signaling. Cancer cells early on develop the ability to proliferate and survive in environments that normally would not support cell replication. Curcumin modulates a host of survival signals through multiple pathways, thereby putting a halt to out-of-control replication.
- Apoptosis. This is the programmed cell death that eliminates dysfunctional cells. Cancer cells lose their ability to die off naturally, which plays a major role in the development of cancer, and in its resistance to conventional treatment. Curcumin switches back on the apoptosis signaling pathway, encouraging over-proliferating cells to die gracefully, rather than continue to grow and spread.
- Growth Factors. A wide variety of growth factors and other molecules can promote cancer cells’ replication. Curcumin directly inhibits many of those molecules, stopping cancer growth in a multitargeted fashion.
- Inflammation. Low-grade inflammation is a powerful promoter of cancer cell growth and survival. Curcumin blocks the pro-inflammatory process at several different points, reducing the overall state of inflammation and slowing cancer development. By blocking the inflammatory master molecule nuclear factor-kappaB (or NF-kB), curcumin blunts cancer-causing inflammation, slashing levels of inflammatory cytokines throughout the body.4,5
- Cancer stem cells. Cancer stem cells are an unusual population of cells within tumors. These cells, like all stem cells, can develop into many different types of mature cells—including new cancer cells. Cancer stem cells are responsible both for new tumor formation and for failures of conventional chemotherapy, because they can survive drugs that kill normal cancer cells. Curcumin has been shown in multiple lab studies to suppress the growth of cancer stem cells. This has the dual benefit of possibly reducing the risk of recurrence after treatment, and also of improving response to therapy of existing malignancies.
- The immune system. The healthy immune system constantly patrols the body, seeking out and destroying incipient cancer cells. As we age, however, the immune system becomes less functional, in a process called immunosenescence. Curcumin supports the body’s immune system by preventing the loss of immune cells that destroy tumors. It also helps overcome tumor-induced resistance to immune destruction, thereby slowing or stopping early cancers naturally.
Studies show that all of these mechanisms, and perhaps many more, are continually active in cancer cells in culture and in animal studies, accounting for today’s great interest in curcumin as a cancer-fighting nutrient.
Promising lab and animal studies have paved the way for a growing series of human studies investigating curcumin’s chemopreventive properties. These now fall into three main categories:
- Studies of curcumin as part of the treatment for existing cancers;
- Studies of curcumin as a means of reducing side effects of chemo- or radiation therapy for existing cancers;
- Studies of curcumin as a means of preventing new cancers.
Let’s examine each category of study separately.
Curcumin in Cancer Treatment
Curcumin has shown promise as a treatment for gastrointestinal cancers. This is because pure curcumin has a low rate of absorption, which is especially beneficial for these cancers because it means that higher levels of the compound stay in the intestinal tract for longer periods of time.
In one study of patients with colorectal cancer, for example, curcumin was administered at a dose of 1,080 mg per day during the period between initial biopsy and surgery (a range of 10 to 30 days).6 At the time of surgery, the supplemented patients experienced numerous benefits, including an increased number of dying tumor cells, an increased expression of a gene that suppresses cancer (called p53), a reduction in blood levels of inflammatory TNF-alpha, and an improvement in body weight.
In another series of colorectal cancer studies, curcumin was shown to improve intracellular free radical scavenging activity (a highly-protective effect), reduce DNA damage, and suppress inflammatory changes.7-9 All of these benefits point to curcumin’s specific treatment effects.
Curcumin has now gone through essential Phase I drug studies, which are aimed at determining the safety and ideal dose of any new therapeutic agent.2 In a group of patients with high-risk or premalignant cancerous lesions, curcumin was found to be tolerable without significant side effects at doses up to 12,000 mg per day.7,10 Beyond its obvious safety, curcumin led to numerous improvements in these patients as well. And in 33% of subjects, the tumors didn’t progress—even when they had not responded to chemotherapy previously.7
Curcumin has made unprecedented headway in attacking a usually lethal type of malignancy: pancreatic cancer. This was seen in a study in which 8,000 mg per day of curcumin treatment produced favorable changes in markers of cancer progression.11 One patient in this study remained stable for 18 months without progression—a nearly unheard-of outcome. Another showed temporary reduction of the existing tumor size by 73%.
Please note that in the many studies cited in this article, either regular curcumin or turmeric powder that contains curcumin was used. Due to the poor absorption of standard curcumin and turmeric powder, very high doses are needed to achieve therapeutic blood levels. Enhanced absorption technologies today enable consumers to use curcumin supplements that provide the equivalent of over 2,000 mg a day of curcumin in just one 400 mg enhanced-absorbing curcumin capsule. Cancer patients often take several 400 mg enhanced-absorbing curcumin capsules daily.
Curcumin and Chemotherapy
Some exciting studies are emerging on curcumin’s potential role as a therapy in addition to standard treatments such as a radiation and chemotherapy. Studies show that not only can it help protect against the damage caused by these treatments, but it can also enhance their effect.
In a laboratory model, when curcumin was given in combination with the chemotherapy drug cisplatin, it significantly reduced the growth of surgically-implanted human head-and-neck tumors in mice.12 And, in human breast, esophageal, and colon cells in culture, curcumin increased the malignant cells’ sensitivity to chemotherapy drugs and to the effects of radiation treatments.13,14
In a study of patients with chronic myeloid leukemia (CML), subjects received either the chemotherapy drug imatinib alone, or imatinib plus curcumin-rich turmeric powder (15 grams per day). After six weeks, the subjects receiving curcumin-plus-imatinib had a significantly greater reduction in a cancer growth factor than the patients treated with the cancer drug alone. Reduction of this growth factor as a result of combined therapy of imatinib and turmeric powder may help in the treatment of chronic myeloid leukemia.15
Curcumin’s ability to help protect against the side effects of these treatments was seen in a study of breast cancer patients receiving radiation therapy. The patients were randomly assigned to receive 2,000 mg of curcumin or a placebo three times daily throughout their course of radiation therapy.16 At the end of the treatment, the patients taking curcumin had significantly less severe radiation damage to their skin and a reduction in skin sloughing. Both of these benefits demonstrate curcumin’s radioprotective effects.
Curcumin Prevents Cancer
It is extremely difficult to design and conduct human studies of cancer prevention. We cannot ethically induce cancer in a group of people and directly study the impact of preventive compounds, as is done in animal studies. Similarly, given the length of the human lifespan, it is not practical to study large groups of people for their entire lives to examine the impact of specific nutrients.
However, two particular kinds of studies—studies of slow-moving cancers or precancerous conditions,17 and studies of biomarkers, which are natural molecules that identify various stages of the transition from normal cells to malignant cells2 —give us important insight into human cancer prevention strategies. Curcumin has been found to be beneficial in both of these kinds of studies, demonstrating its benefit in human cancer prevention.
Curcumin’s impact on precancerous conditions can be seen in a study of people with “monoclonal gammopathy of undetermined significance,” and “smoldering multiple myeloma.”17 Both of these conditions are disorders of antibody-producing cells (these are immune cells that help to identify and neutralize pathogens), and both can progress to a potentially fatal blood cancer called multiple myeloma. A strong predictor of the likelihood of these conditions progressing to multiple myeloma is found through the detection of an abnormal ratio of certain proteins produced by the premalignant cells.
By the end of the study period, supplemented subjects showed a significant decrease in the abnormal protein ratio, and also in the presence of other “useless” proteins produced by premalignant cells.17 Treated subjects also showed a significant reduction in markers of bone resorption (bone breakdown), a problem that occurs as multiple myeloma progresses and erodes into bony areas. This shows that curcumin could have the potential to slow the disease process from a premalignant to a malignant state.
In a remarkably similar finding in prostate cancer, a supplement of curcumin plus soy isoflavones was effective at decreasing levels of prostate-specific antigen (PSA, a biomarker of prostate cancer activity) in men with the highest levels at baseline, but with no detectable cancer yet.18 These two studies together suggest that curcumin’s cancer-preventive effects may be most evident in more advanced precancerous conditions.
Colon cancer is another malignancy in which prevention can be studied because it is frequently first detectable as precancerous polyps or collections of abnormal cells called aberrant crypt foci. These represent one of the earliest changes seen in the colon that may lead to cancer.
In a study of patients with familial adenomatous polyposis (an inherited condition in which people develop multiple polyps that progress to cancer), taking curcumin (480 mg) and quercetin (20 mg) three times a day reduced the size and number of polyps by more than half.19 Another study demonstrated that taking 4,000 mg of curcumin per day for 30 days significantly reduced the number of aberrant crypt foci by 40%, again demonstrating curcumin’s power to prevent cancer progression.20
Finally, a number of other studies have shown that curcumin reduces cancer-associated biomarkers, such as inflammatory molecules and oxidative damage, in patients having head-and-neck cancers, skin cancers, and tropical pancreatitis, an inflammatory disorder that can lead to pancreatic cancer.21-25
Curcumin offers a multitargeted approach to cancer prevention that may also extend to treatment and mitigation of treatment side effects.
Curcumin operates by numerous independent mechanisms, most of which match up to a specific step in cancer development. This multitargeted approach is critical in a disease as complex and varied as cancer.
Studies show that curcumin has anticancer properties in malignancies as varied as colorectal, breast, prostate, pancreas, ovary, and others. Boosting curcumin’s bioavailability by reconstituting it with natural oils and other compounds from the turmeric root is a promising means of increasing its effectiveness throughout the body.
Anyone with a strong personal or family history of cancer should consider routine supplementation with this versatile natural compound, which can attack cancer at its most fundamental roots.
Curcumin’s ready availability, low cost, and low toxicity make it live up to its name as an “ideal chemopreventive agent.”
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
- Available at: http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-047079.pdf. Accessed May 31, 2016.
- Park W, Amin AR, Chen ZG, et al. New perspectives of curcumin in cancer prevention. Cancer Prev Res (Phila). 2013;6(5):387-400.
- Devassy JG, Nwachukwu ID, Jones PJ. Curcumin and cancer: barriers to obtaining a health claim. Nutr Rev. 2015;73(3):155-65.
- Bachmeier BE, Killian P, Pfeffer U, et al. Novel aspects for the application of Curcumin in chemoprevention of various cancers. Front Biosci (Schol Ed). 2010;2:697-717.
- Sikora E, Bielak-Zmijewska A, Mosieniak G, et al. The promise of slow down ageing may come from curcumin. Curr Pharm Des. 2010;16(7):884-92.
- He ZY, Shi CB, Wen H, et al. Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer Invest. 2011;29(3):208-13.
- Sharma RA, McLelland HR, Hill KA, et al. Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res. 2001;7(7):1894-900.
- Sharma RA, Euden SA, Platton SL, et al. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res. 2004;10(20):6847-54.
- Garcea G, Berry DP, Jones DJ, et al. Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol Biomarkers Prev. 2005;14(1):120-5.
- Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001;21(4b):2895-900.
- Dhillon N, Aggarwal BB, Newman RA, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res. 2008;14(14):4491-9.
- Duarte VM, Han E, Veena MS, et al. Curcumin enhances the effect of cisplatin in suppression of head and neck squamous cell carcinoma via inhibition of IKKbeta protein of the NFkappaB pathway. Mol Cancer Ther. 2010;9(10):2665-75.
- Hartojo W, Silvers AL, Thomas DG, et al. Curcumin promotes apoptosis, increases chemosensitivity, and inhibits nuclear factor kappaB in esophageal adenocarcinoma. Transl Oncol. 2010;3(2):99-108.
- Sandur SK, Deorukhkar A, Pandey MK, et al. Curcumin modulates the radiosensitivity of colorectal cancer cells by suppressing constitutive and inducible NF-kappaB activity. Int J Radiat Oncol Biol Phys. 2009;75(2):534-42.
- Ghalaut VS, Sangwan L, Dahiya K, et al. Effect of imatinib therapy with and without turmeric powder on nitric oxide levels in chronic myeloid leukemia. J Oncol Pharm Pract. 2012;18(2):186-90.
- Ryan JL, Heckler CE, Ling M, et al. Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients. Radiat Res. 2013;180(1):34-43.
- Golombick T, Diamond TH, Manoharan A, et al. Monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and curcumin: a randomized, double-blind placebo-controlled cross-over 4g study and an open-label 8g extension study. Am J Hematol. 2012;87(5):455-60.
- Ide H, Tokiwa S, Sakamaki K, et al. Combined inhibitory effects of soy isoflavones and curcumin on the production of prostate-specific antigen. Prostate. 2010;70(10):1127-33.
- Cruz-Correa M, Shoskes DA, Sanchez P, et al. Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clin Gastroenterol Hepatol. 2006;4(8):1035-8.
- Carroll RE, Benya RV, Turgeon DK, et al. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila). 2011;4(3):354-64.
- Kim SG, Veena MS, Basak SK, et al. Curcumin treatmentsuppresses IKKbeta kinase activity of salivary cells of patients with head and neck cancer: a pilot study. Clin Cancer Res. 2011;17(18):5953-61.
- Durgaprasad S, Pai CG, Vasanthkumar, et al. A pilot study of the antioxidant effect of curcumin in tropical pancreatitis. Indian J Med Res. 2005;122(4):315-8.
- Rai B, Kaur J, Jacobs R, et al. Possible action mechanism for curcumin in pre-cancerous lesions based on serum and salivary markers of oxidative stress. J Oral Sci. 2010;52(2):251-6.
- Tandon RK, Garg PK. Tropical pancreatitis. Dig Dis. 2004;22(3):258-66.
- Zhu S, Moore TW, Lin X, et al. Synthetic curcumin analog EF31 inhibits the growth of head and neck squamous cell carcinoma xenografts. Integr Biol (Camb). 2012;4(6):633-40.
- Marczylo TH, Verschoyle RD, Cooke DN, et al. Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine. Cancer Chemother Pharmacol. 2007;60(2):171-7.
- Yue GG, Cheng SW, Yu H, et al. The role of turmerones on curcumin transportation and P-glycoprotein activities in intestinal Caco-2 cells. J Med Food. 2012;15(3):242-52.
- Lao CD, Ruffin MTt, Normolle D, et al. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med. 2006;6:10.
- Antony B, Merina B, Iyer VS, et al. A pilot cross-over study to evaluate human oral bioavailability of BCM-95CG (Biocurcumax), a novel bioenhanced preparation of curcumin. Indian J Pharm Sci. 2008;70(4):445-9.