The Root of Cancer Prevention is Turmeric: A Research Review
A comparison of age-adjusted cancer rates in Australia and India in 2022 illustrates a clear difference between the two countries. Assessing differences in dietary practices may expose part of the reason why.
Australia:1 507 cases per 100,000 people
India:2 107 per 100,000 people
A large proportion of Indians are vegetarian. Vegetarianism has been associated with decreased risk of some cancers,3 but not others.4 Dietary fibre and fat intake should also be taken into consideration when interpreting this data, but there is one key factor that should not be overlooked in terms of cancer prevention: the abundance of spices consumed in Indian food and the Ayurvedic diet. One ingredient in common Indian curry and a spice with potent anti-inflammatory activities is Turmeric.3 Diet surveys in India, show the use of Turmeric averages around 0.24 g/person/day among high-income households, and around 0.49 g/person/day among low-income households. In rural areas of India, consumption is around 0.73 g/person/day. Another estimation for Turmeric consumption by some adults in India puts it as high as 4 g/person/day, which would supply approximately 80 to 200 mg of curcumin.5
Turmeric, through its major active constituent curcumin, has the potential to inhibit the formation and spread of cancerous cells through a range of mechanisms. Some of the key mechanisms are explored below.
Antioxidant Effects
The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates cellular resistance to oxidative stress by controlling the expression of an array of antioxidant response element (ARE)-dependent genes.6 In part, the chemopreventive and antiproliferative effects of curcumin are attributed to its effects on the Nrf2 pathway, as demonstrated by studies in breast and prostate cancer cells.7
In vivo, curcumin has been shown to activate the Nrf2 pathway, modulate inflammatory molecules and induce tumour suppressor gene p53 (Trp53) expression.8 Crucial for genome stability, p53 acts as a sensor of cellular stress and controls several genes that play a role in cell cycle arrest, cellular senescence, deoxyribonucleic acid (DNA) repair, and apoptosis. Furthermore, p53 can activate autophagy, involved in tumour suppression. The majority of the human cancer cells exhibit inactivation of the p53 pathway.9
Antiproliferative and Antimetastatic Activity
Nuclear factor-kappa B (NFκB) is a transcription factor that controls the expression of proteins in a variety of cell signalling pathways that lead to tumorigenesis and inflammation. Aberrant NFκB signalling plays a major role in the pathogenesis of several types of cancers.
Many research groups have shown that curcumin inhibits cancer cell proliferation, survival, invasion, metastasis, chemoresistance, radioresistance, and angiogenesis of various cancers (e.g., pancreatic, colon and ovarian cancer, and multiple myeloma) by modulating different targets that are regulated by NF-κB. Furthermore, curcumin’s ability to inhibit the expression of cyclin D1, cyclooxygenase (COX-2), matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), and CXC chemokine receptor 4 (CXCR4) – all involved in cancer development – may be a result of its inhibitory effect on NF-κB activation.
Epidermal growth factor receptor (EGFR) is a complex signal transduction cascade involved in the modulation of cell proliferation. Curcumin’s potential to inhibit the growth, invasion, and metastasis of cancer cells via the downregulation of EGFR expression is well documented. Beneficial effects on this target have been demonstrated in brain, oral, lung, pancreatic, hepatocellular, colon, bladder, breast, ovarian, and cervical cancer cells and animal models.7
Apoptosis- and Autophagy-Inducing
Dysregulated apoptosis and autophagy are implicated in the proliferation, invasion, and metastasis of tumour cells.10 Research shows that curcumin can influence such signalling pathways in lung, hepatocellular, breast, thyroid, pancreatic, colon,7 chronic myeloid leukaemia, malignant glioma, and oesophageal cancer cells.11
Antiangiogenic Effects
Vascular endothelial growth factor (VEGF) is a key angiogenic factor in tumours, participating in the initial stage of tumour development, progression and metastasis.12 In other words, tumour vascularisation is dependent upon VEGF.13 In human intestinal microvascular endothelial cells, curcumin can inhibit multiple stages of angiogenesis induced by VEGF.14
Turmeric for Cancer Prevention
Cancer rates in India are lower than those in Western countries.3 Differences in dietary practices, such as the consumption of Turmeric, may contribute to differences in disease rates. The various mechanisms by which curcumin can potentially suppress the development and spread of cancer cells demonstrates the versatility and value of natural chemopreventive agents. Evidently, the nutritional counselling provided by natural medicine practitioners has the potential to shape the health of cancer patients, now and into the future.
References
1. Australian Institute of Health and Welfare. Cancer [Internet]. Canberra: Australian Government; 2022 [cited 2023 June 1]. Available from: https://www.aihw.gov.au/reports/australias-health/cancer
2. Sathishkumar K, Chaturvedi M, Das P, Stephen S, Mathur P. Cancer incidence estimates for 2022 & projection for 2025: result from National Cancer Registry Programme, India. Indian J Med Res. 2022;156(4&5):598-607. DOI: 10.4103/ijmr.ijmr_1821_22
3. Sinha R, Anderson DE, McDonald SS, Greenwald P. Cancer risk and diet in India. J Postgrad Med. 2003;49(3):222-228.
4. Gathani T, Barnes I, Ali R, Arumugham R, Chacko R, Digumarti R, et al. Lifelong vegetarianism and breast cancer risk: a large multicentre case control study in India. BMC Womens Health. 2017 Jan;17(1):6. DOI: 10.1186/s12905-016-0357-8
5. Hutchins-Wolfbrandt A, Mistry AM. Dietary turmeric potentially reduces the risk of cancer. Asian Pac J Cancer Prev. 2011;12(12):3169-3173.
6. Ma Q. Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol. 2013;53:401-426. DOI: 10.1146/annurev-pharmtox-011112-140320
8. Das L, Vinayak M. Long term effect of curcumin in restoration of tumour suppressor p53 and phase-II antioxidant enzymes via activation of Nrf2 signalling and modulation of inflammation in prevention of cancer. PLoS One. 2015;10(4):e0124000. DOI: 10.1371/journal.pone.0124000
9. Feroz W, Sheikh AMA. Exploring the multiple roles of guardian of the genome: p53. Egypt J Med Hum Genet. 2020;21(49). DOI: 10.1186/s43042-020-00089-x
10. Rascio F, Spadaccino F, Rocchetti MT, Castellano G, Stallone G, Netti GS, et al. The pathogenic role of PI3K/AKT pathway in cancer onset and drug resistance: an updated review. Cancers (Basel). 2021 Aug;13(16):3949. DOI: 10.3390/cancers13163949
11. Zhang X, Chen LX, Ouyang L, Cheng Y, Liu B. Plant natural compounds: targeting pathways of autophagy as anti-cancer therapeutic agents. Cell Prolif. 2012 Oct;45(5):466-476. DOI: 10.1111/j.1365-2184.2012.00833.x
12. Yang Y, Cao Y. The impact of VEGF on cancer metastasis and systemic disease. Semin Cancer Biol. 2022 Nov;86(Pt 3):251-261. DOI: 10.1016/j.semcancer.2022.03.011
13. Carmeliet P. VEGF as a key mediator of angiogenesis in cancer. Oncology. 2005;69 Suppl 3:4-10. DOI: 10.1159/000088478
14. Binion DG, Otterson MF, Rafiee P. Curcumin inhibits VEGF-mediated angiogenesis in human intestinal microvascular endothelial cells through COX-2 and MAPK inhibition. Gut. 2008 Nov;57(11):1509-1517. DOI: 10.1136/gut.2008.152496
