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Currently, numerous preclinical findings suggest resveratrol as a promising compound for cancer prevention and treatment.
A chemopreventive agent (preventing cancer) can operate via different mechanisms, such as the inhibition of the metabolic activation of carcinogenic compounds, the stimulation of reactive metabolite detoxification, the prevention of their interaction with cell DNA and the suppression of tumor progression. Resveratrol is able to act on each of these mechanisms and it can simultaneously inhibit promutagen bioactivation, stimulate carcinogen detoxification and prevent the organism against the adverse effects of diverse environmental toxicants.
Resveratrol may also possess a chemotherapeutic potential – that is to help treat cancer. It suppresses growth of various cancer cell lines, partly by an inhibition of DNA polymerase and ribonucleotide reductase and partly by inducing cell cycle arrest or apoptosis (killing of cells when necessary). Intraperitoneal injections also decrease the number of tumor cells in a Yoshida AH-130 ascite hepatoma rat model.
Dr. Jang and his collaborators published cutting-edge research results in Science in January 1977, considered the top-rated peer-reviewed journal. Their work showed that resveratrol functions as a potent anti-mutagen. Its beneficial effects included the induction of Phase II drug-metabolizing enzymes (anti-initiation activity), inhibition of cyclooxygenase and hydroperoxidase functions (anti-promotion activity), and the induction of human promyelocytic-leukemic cell differentiation (anti-progression activity).
Resveratrol inhibited cancer initiation by reducing in vitro free radical formation when human leukemia cells were treated with TPA effective dose, inhibiting the mutagenic response when Salmonella typhimurium cells were treated with a noxious polycyclic aromatic hydrocarbon DMBA, and inducing quinone reductase activity in cultured mouse hepatoma cells. This last observation is highly significant because Stage II enzymes such as quinone reductase are capable of detoxifying carcinogens. This might all sound way over the top – but is simply means that in the studies done, resveratrol showed some amazing capabilities in fighting cancer.
Resveratrol also inhibited cancer promotion in mice by inhibiting cyclooxygenase activity of COX-1 and hydroperoxidase activity of COX-1 and COX-2 and reducing pedal edema both in the acute (3 to 7 hours) and chronic (24 to 144 hours) phases.
Cyclooxygenase activity inhibition is relevant to cancer chemoprevention because it catalyzes the conversion of arachidonic acid to pro-inflammatory substances, which can stimulate tumor cell growth and suppress immune surveillance. Cyclooxygenase can also activate carcinogens to forms that damage cellular material.
Considerable evidence has accumulated suggesting that COX-2 is important in tumorigenesis and that targeted inhibition of CQX-2 may be an innovative approach to preventing cancer and treating inflammation.
Treatment of human mammary epithelial cells with phorbol ester (PMA)- mediated induction of COX-2 induces a marked increase in production of prostaglandin E2. The enhanced synthesis of prostaglandins can favor the growth of malignant cells by increasing cell proliferation. Resveratrol suppresses PMA-mediated increases in COX-2 mRNA and protein. Additionally, nuclear runoffs revealed increased rates of COX-2 transcription after treatment with PMA, an effect that also was inhibited by resveratrol. In this way, resveratrol can serve as a potential natural product to prevent cancer by targeted inhibition of COX-2.8
Resveratrol also delayed the onset of cancer progression by inducing expression of nitroblue tetrazolium reduction activity, a marker of granulocyte formation, and nonspecific acid esterase activity, a marker of macrophage formation; and inhibiting incorporation of [3H] thymidine, a marker of terminal differentiation to a non-proliferative phenotype.
Resveratrol was also found to possess chemopreventive activity by inhibiting ribonucleotide reductase and cyclooxygenase-28 and by inhibiting cellular events associated with cell proliferation and tumor initiation, promotion, and progression.
Ribonucleotide reductase is a protein enzyme complex that catalyzes the reduction of ribonucleotide into the deoxyribonucleotides required for DNA synthesis. Basically, this enzyme provides proliferating cells with the deoxynucleotides required for DNA synthesis. By inhibiting this enzyme, resveratrol exhibits antiproliferating activity and so inhibits cancer cell proliferation and differentiation.
A very significant decrease (25 percent) in the tumor cell content resulted when rats inoculated with a fast-growing tumor (the Yoshida AH-130 ascites hepatoma) were given resveratrol in vivo. The researchers were able to show that resveratrol caused apoptosis (programmed cell death) in the tumor cell population, which resulted in a decreased cell number of cancer cells.
Resveratrol was also found to induce apoptotic (programmed) cell death in human leukemic HL-60 cells and in T47D breast carcinoma cells at doses minimally toxic to normal peripheral blood lymphocytes. Resveratrol-induced apoptosis is mediated via caspase activation inhibitable by tetrapeptide caspase inhibitors.
Furthermore, resveratrol enhances CD95L expression and induces CD95, signaling dependent cell death in both tumor cell lines. The chemopreventive activity of resveratrol could be explained by the induction of CD95-dependent apoptotic cell death in tumor cells, leading to the inhibition of tumor initiation and progression.
Dr. Ragione and his colleagues investigated the activity of resveratrol on proliferation and differentiation of the human promyelocitic HL-60 cells. A low concentration causes a complete arrest of proliferation and a rapid induction of differentiation towards a myelo-monocytic phenotype. Resveratrol induces a complete and reversible cell cycle arrest at the S-phase checkpoint. These studies demonstrated that resveratrol is a potential candidate for the development of anti-cancer treatment as well as for inhibiting lymphocyte proliferation during immunosuppressive therapies.
From the above you will see that a variety of trials have been done on cancer as such, but a large volume of research has also been undertaken on how resveratrol influence cancer cells in the human breast cells, and although it cannot be claimed yet that resveratrol arrests the development of breast cancer, or is an effective treatment for breast cancer – all the research points to very interesting and positive effects that may still need further investigation. It can however be safely assumed that resveratrol is a supplement of choice when battling with this disease. CLINICAL REFERENCES
One of the cancers that men fear most must be prostate cancer, as it can have such a direct influence on their sexual functioning. It must however be kept in mind that if prostate cancer is detected and treated early, the prognosis is excellent.
A variety of trials and research have also been done on the positive effect that resveratrol has on prostate cancer – and although more studies may be needed to conclusively show that there is a place for resveratrol in the treatment of prostate cancer, it can be fairly taken that resveratrol can be most beneficial when fighting prostate cancer. CLINICAL REFERENCES