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Old 02-07-2008, 04:33 PM
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Default Resveratrol-induced apoptosis in acute human leukemia

Acute leukemia, resveratrol

While chemotherapy has produced a dramatic improvement in survival of patients with acute leukemia, researchers at the University of Milan lament at the inevitable relapse of this form of cancer as drug resistance sets in. Writing in the Journal of Biochemical Pharamacology, these researchers note that the cellular machinery that makes tumor cells eventually die off and be replaced by new healthy cells is dysfunctional in cancer cells. Cancer cells become immortal. This is particularly the problem in acute leukemia. So these researchers in Italy began a search for a molecule that would induce the leukemia cells to die off normally. They report that resveratrol, known as a red wine molecule, markedly and unequivocally causes drug-resistant leukemia cells to die off in a normal fashion. Given that patients with acute leukemia face an inevitable fate, this striking discovery should prompt researchers to hasten their investigation of this natural molecule. Even with the impetus to move forward and produce timely research studies, it may be years before resveratrol is used in the treatment of acute leukemia. For many patients with acute leukemia, they haven�t the time to wait. Resveratrol is a natural molecule that is available as a dietary supplement. In modest doses, less than 500 milligrams, it produces few if any side effects, though it may not mix well with many prescription medications. But it does enhance the effect of many anti-cancer drugs. Resveratrol is more bioavailable when combined with another red-wine molecule, quercetin and has more capacity to kill tumor cells when combined with another natural molecule called IP6, found in rice bran. For more information about cancer therapies, visit www.thecancerbook.com

Biochemical Pharmacology 2007 Dec 3;74(11):1568-74.
Resveratrol-induced apoptosis in human T-cell acute lymphoblastic leukaemia MOLT-4 cells.
Department of Biomedical Science and Technology, University of Milano, Italy.
Resveratrol (RES) is a natural occurring phytoalexin that has been shown to have chemopreventive activity. Resveratrol acts both by suppressing cell proliferation and inducing apoptosis in a variety of cancer cell lines. In this study, we show that RES induces apoptosis in MOLT-4 acute lymphoblastic leukaemia cells by modulating three different pathways that regulate cells survival and cell death. We show for the first time that RES inhibits the survival signalling pathways Notch and their down stream effector and modulates the operation of interacting signalling systems. It induces an increase in the levels of the pro-apoptotic proteins p53, its effector p21waf and Bax. We also show that RES inhibits the PI3K/Akt pathway and activates Gsk-3beta. The data presented here demonstrate unequivocally that RES induces apoptosis by inhibiting the Notch pathway and markedly influencing the operation of the interacting apoptosis pathways mediated by p53 and PI3K/Akt. These data support findings from other laboratories that have suggested the use of RES as a chemopreventive agent. Here, we have identified potential signalling pathways influenced by RES and this could lead to the identification of the targets of RES-induced apoptosis and growth control.
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