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Resveratrol induced apoptosis in cancer cells
Resveratrol has been found to induce apoptosis in cancer cells through four significant pathways: the heat shock protein 70(Hsp70), adenosine monophosphate activated protein kinase (AMPK), Sirtuin 1 (SIRT1), and survivin pathways. Due to its ability to bind to multiple targets closely related to carcinogenesis, resveratrol targets various oncoproteins without causing harm to normal, healthy cells. By doing this, resveratrol is able to induce apoptosis in regular cancer cells as well as in drug resistant cancer cells such as chronic myelogenous leukemia (CML) and HT-29 human colon cancer cells.

Heat shock protein 70 pathway
The transcription of Hsp70 is under the control of heat shock factor 1 (HSF1). Hsp70 causes cells to evade apoptosis and is transcribed when HSF1 senses cellular stress. When this mechanism is disrupted and does not switch on and off at the appropriate times, Hsp70 becomes over-expressed, which leads to antiapopticity and malignancy of cancer cells. A large number of cancers have been linked to the over-expression of Hsp70.

Resveratrol has been found to block the HSF1 transcriptional activity of Hsp70. Addition of resveratrol to CML K562 cells lowers the levels of HSF1 activity which in turn causes less Hsp70 to be produced, inducing apoptosis.

The high endogenous levels of Hsp70 in CML K562 cells have become a problem when it comes to chemotherapeutic drug resistance. When 17-AAG, a chemotherapeutic drug, is added to K562 cells, reduced levels of Hsp90 are observed, which elevates levels of Hsp70, causing the cells to become antiapoptotic and resistant to this particular treatment. However, when 17-AAG plus resveratrol are added to K562 cells, both Hsp90 and Hsp70 levels are reduced causing apoptosis within the cells.

Adenosine monophosphate activated protein kinase pathway
Resveratrol has been found to activate and increase levels of AMPK in breast cancer cells, inducing apoptosis within the cells. One target of the AMPK pathway is the mammalian target of rapamycin (mTOR) pathway. Increases in mTOR activity, a characteristic common in many types of cancer due to the disregulation of the AMPK signaling pathway, lead to increased cell proliferation and the formation of antiapoptotic cancer cells. Resveratrol induces phosphorylation of AMPK and decreases levels of mTOR phosphoylation, which deactivates mTOR and induces apoptosis.

An in vivo model was used to prove that resveratrol induces AMPK protein levels in mice. When mice are injected with MDA-MB-231 breast cancer cells and treated with either resveratrol or a placebo, higher levels of AMPK are observed in the tumors that have been exposed to resveratrol. This indicates that resveratrol's apoptotic ability can be applied to a living model.

Chemotherapeutic drug resistance of colon cancer cells is a difficult obstacle to overcome when it comes to cancer treatment. Resveratrol can overcome the resistance of HT-29 colon cancer cells against the chemotherapy drug, Etoposide. Etoposide on its own cannot inhibit the proliferation of HT-29 cells, but when combined with resveratrol, a dramatic increase in AMPK activation is observed, inducing apoptosis within the cells.

Sirtuin 1 pathway
Resveratrol induces the expression of SIRT1 in many types of cancer cells, causing apoptosis. When MDA-MB-231 breast cancer tumors are taken from mice that have been treated with either resveratrol or a placebo and tested for SIRT1, SIRT1 levels are found to be higher in tumors taken from mice that have been treated with resveratrol.

Apoptosis induced by AMPK activation is dependent on the activation of SIRT1 by resveratrol. Addition of resveratrol to MCF-7 breast cancer cells in the presence and absense of nicotinamide, a SIRT1 inhibitor, shows that lower levels of AMPK are present when SIRT1 cannot be expressed. This indicates that SIRT1 must be activated in order to have the AMPK activation that induces apoptosis.

Survivin pathway
Resveratrol has been found to decrease levels of survivin, an antiapoptotic protein found in cancer cells, through activation of SIRT1. Topically applied resveratrol on mouse skin upregulates SIRT1 levels which inhibits survivin expression and induces apoptosis in mouse skin cells that have been mutated due to exposure to UV-B radiation.

Future applications of resveratrol in cancer treatment and prevention
Resveratrol causes apoptotic effects in cancer cells by downregulating Hsp70 protein expression in CML K562 cell lines and survivin levels in mouse skin exposed to UV-B radiation, as well as upregulating the expression of SIRT1 in many types of cancer cells and AMPK levels in HT-29 colon cancer cells that have previously been resistant to Etoposide. Targeting of the Hsp70, survivin, SIRT1, and/or AMPK pathways by resveratrol may have beneficial clinical applications for cancer patients.

Excessive mutations caused by UV-B radiation in the DNA of skin cells often lead to the formation of melanoma. Resveratrol could help to prevent melanoma by targeting and downregulating the antiapoptotic protein, survivin, and inducing apoptosis in these mutated cells. The production of sunscreens and lotions with resveratrol as an ingredient may be a promising product to help prevent melanomas caused by DNA mutations due to UV-B radiation.