• Marcio Alvarez-Silva, PhD

Resveratrol, an anti-cancer element in fruit and wine

In oncology, in addition to nourishing the patient, food is important in multiple aspects.

In recent years many scientific studies have pointed to the role of bioactive substances in food as having important effects on human physiology. In some cases these substances can be useful in combating some diseases, these bioactive substances are classified as nutraceuticals [1].

One of these bioactive substances is resveratrol.

Resveratrol can be found in some fruits that are part of the human diet, including peanuts, grapes, wine, blueberries, pistachios, plums, blackberries and cramberry [2]. However, red wine is the main source of resveratrol. The amount of resveratrol in red wine can reach 580 μg per 100 mL of the drink [3].

It has been shown that the use of resveratrol has many beneficial effects on health. The first reports of the bioactive effects of resveratrol were about its role in cardiovascular health, through a phenomenon that was coined by Renaud and Lorgeril as a "French paradox" [4]. In this work, the authors observed that, despite the fact that the French have a high intake of saturated fats in their diet, they have a lower incidence (about 40%) of coronary diseases than the rest of Europe. This was attributed to the regular consumption of red wine by the French population.

Resveratrol has attracted the attention of scientists for presenting important therapeutic properties, including: antidiabetic, antiallergic, cardioprotective, neuroprotective, antiobesity, anti-inflammatory, antioxidant and anti-aging [5-10]. Based on its extensive activity in disease prevention, resveratrol was classified as an important nutraceutical [11].

In 1997, Jang and collaborators [12] demonstrated in a pioneering study that resveratrol inhibits carcinogenesis, using an experimental model of skin cancer. This study quickly opened up the possibility of resveratrol acting as an important anti-cancer substance. From this work, many publications demonstrating the antitumor effects of resveratrol were followed in the scientific literature.

Resveratrol is capable of reducing the proliferation and formation of malignant tumors in vitro and in vivo [13-15]. Studies prove that resveratrol inhibits the growth of malignant cells in several types of cancer and leukemia, including skin, lung, liver, prostate, breast, ovary, and colon cancer [16-24]. Numerous scientific publications demonstrate that the regular consumption of resveratrol can be used as an important protector for the development and progression of several types of cancer, including reducing the metastases [25-27]. A clinical study showed that high daily doses of resveratrol (up to 5.0 grams/day) were safe in volunteers [28]. Therefore it is possible to regularly consume resveratrol without adverse effects and with great advantages for health.

These studies show that resveratrol can be an important ally in the prevention of several diseases, including cancer. The regular consumption of resveratrol can have an important preventive effect on human health.

When the tumor is present in the patient, resveratrol has also been shown to be effective when used together with the drugs in chemotherapy, with important effects on the general improvement of the patient during treatment. It has been reported that resveratrol can increase the efficacy of chemotherapeutic drugs in several tumor models without affecting or causing damage to normal cells [29]. The combination of cisplatin and resveratrol in hepatocellular carcinoma had additive and/or synergistic effects that increased the chemosensitization of cancerous cells to chemotherapy, potentiating its effect to eliminate malignant cells [30]. The use of resveratrol combined with 5-Fluorouracil enhanced the action of this chemotherapy in colorectal cancer cells, improving its therapeutic efficacy [31]. The combination of resveratrol with melphalan or doxorubicin increased the cytotoxic potential of these chemotherapeutic agents in breast cancer cells, eliminating the malignant cells with a magnitude higher than the chemotherapeutic agents isolated [32-34]. It was also demonstrated that resveratrol potentiated the effect of etoposide in lung cancer cells [35] and that the combination of resveratrol and gencitabine improves the action of this chemotherapy in pancreatic cancer cells [36].

These evidences show the possibility of resveratrol supplementation with chemotherapeutic drugs during the treatment of cancer, which can effectively improve the effect of the drugs on the patient, in order to achieve therapeutic success in the fight against the disease.

The scientific literature has shown that resveratrol can be an important ally in the fight against cancer, since it can be systematically used to help prevent the disease.

When the disease is established, resveratrol can have an important action when associated with chemotherapy treatment, improving the action of medicines.

However, it is always important to emphasize that it is necessary the medical accompaniment during the whole curative process and that the patient never leaves or abandons the chemotherapeutic treatment.

There is no evidence that the resveratrol or any other nutraceutical can eliminate by itself a tumor already developed in the patient, without the help of chemotherapeutic drugs. What the scientific literature shows is that resveratrol improves the efficacy of these drugs in the treatment of established tumors in the patient.

It is always important to emphasize that a balanced diet rich in vegetables such as fruits and vegetables is an important source of nutraceuticals that can help prevent cancer as well as several other diseases.

References:

1. DeFelice, S.L., The nutraceutical revolution: its impact on food industry R&D. Trends in Food Science & Technology, 1995. 6(2): p. 59-61. 2. Chachay, V.S., et al., Resveratrol – pills to replace a healthy diet? British Journal of Clinical Pharmacology, 2011. 72(1): p. 27-38. 3. Chedea, V.S., et al., Resveratrol: from diet to topical usage. Food & Function, 2017. 8(11): p. 3879-3892. 4. Renaud, S. and M. de Lorgeril, Wine, alcohol, platelets, and the French paradox for coronary heart disease. The Lancet, 1992. 339(8808): p. 1523-1526. 5. Baur, J.A., et al., Resveratrol improves health and survival of mice on a high-calorie diet. Nature, 2006. 444(7117): p. 337-342. 6. Xia, N., et al., Antioxidant effects of resveratrol in the cardiovascular system. British Journal of Pharmacology, 2017. 174(12): p. 1633-1646. 7. Rauf, A., et al., A comprehensive review of the health perspectives of resveratrol. Food & Function, 2017. 8(12): p. 4284-4305. 8. Kulkarni, S.S. and C. Cantó, The molecular targets of resveratrol. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2015. 1852(6): p. 1114-1123. 9. Nawaz, W., et al., Therapeutic Versatility of Resveratrol Derivatives. Nutrients, 2017. 9(11): p. 1188. 10. Bhullar, K.S. and B.P. Hubbard, Lifespan and healthspan extension by resveratrol. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2015. 1852(6): p. 1209-1218. 11. Sauer, S. and A. Plauth, Health-beneficial nutraceuticals—myth or reality? Applied Microbiology and Biotechnology, 2017. 101(3): p. 951-961. 12. Jang, M., et al., Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes. Science, 1997. 275(5297): p. 218-220. 13. Vendrely, V., et al., Resveratrol and capsaicin used together as food complements reduce tumor growth and rescue full efficiency of low dose gemcitabine in a pancreatic cancer model. Cancer Letters, 2017. 390: p. 91-102. 14. Saud, S.M., et al., Resveratrol prevents tumorigenesis in mouse model of Kras activated sporadic colorectal cancer by suppressing oncogenic Kras expression. Carcinogenesis, 2014. 35(12): p. 2778-2786. 15. Baur, J.A. and D.A. Sinclair, Therapeutic potential of resveratrol: the in vivo evidence. Nature Reviews Drug Discovery, 2006. 5(6): p. 493-506. 16. BHAT, K.P.L. and J.M. PEZZUTO, Cancer Chemopreventive Activity of Resveratrol. Annals of the New York Academy of Sciences, 2002. 957(1): p. 210-229. 17. Tessitore, L., et al., Resveratrol depresses the growth of colorectal aberrant crypt foci by affecting bax and p21CIP expression. Carcinogenesis, 2000. 21(8): p. 1619-1622. 18. Hsieh, T.-c. and J.M. Wu, Differential Effects on Growth, Cell Cycle Arrest, and Induction of Apoptosis by Resveratrol in Human Prostate Cancer Cell Lines. Experimental Cell Research, 1999. 249(1): p. 109-115. 19. 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This article was published in Understanding Cancer magazine, July 12, 2019.

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