resveratrol (in wine, grape juice, etc) causes breast cancer cell death via effect on

[Lani]

mitochondria, calcium metabolism

Mol Pharmacol. 2007 Sep 11; [Epub ahead of print]
Mitochondria, Calcium, and Calpain are Key Mediators of Resveratrol-Induced Apoptosis in Breast Cancer.

Sareen D, Darjatmoko SR, Albert DM, Polans AS.
University of Wisconsin - Madison.
Resveratrol (RES), a natural plant polyphenol, has gained interest as a non-toxic chemopreventive agent capable of inducing tumor cell death in a variety of cancer types. However, the early molecular mechanisms of RES-induced apoptosis are not well defined. Using the human breast cancer cell lines MDA-MB-231 and MCF-7, we demonstrate that RES is anti-proliferative and induces apoptosis in a concentration- and time-dependent manner. Preceding apoptosis, RES instigates a rapid dissipation of mitochondrial membrane potential (DeltaPsim) by directly targeting mitochondria. This is followed by release of cytochrome c and Smac/DIABLO into the cytoplasm and substantial increase in the activities of caspases-9 and -3 in MDA-MB-231 cells. Additionally, live cell microscopy demonstrates that RES causes an early biphasic increase in the concentration of free intracellular calcium ([Ca(2+)]i), likely resulting from depletion of the endoplasmic reticulum (ER) stores in breast cancer cells. In caspase-3 deficient MCF-7 cells apoptosis is mediated by the Ca(2+)- activated protease, calpain, leading to the degradation of plasma membrane Ca(2+)-ATPase isoform 1 (PMCA1) and fodrin; the degradation is attenuated by buffering [Ca(2+)]i and blocked by calpain inhibitors. Mitochondrial permeability transition pore antagonists also blocked calpain activation. In vivo mouse xenograft studies demonstrate that RES treatment inhibits breast cancer growth with no systemic toxicities. Collectively, these results suggest a critical role for mitochondria not only in the intrinsic apoptotic pathway but also in the Ca(2+) and calpain-dependent cell death initiated by RES. Thus, RES may prove useful as a non-toxic alternative for breast cancer treatment.
PMID: 17848600 [PubMed - as supplied by publisher]

[Joanne S]

Resveratrol could be the next miracle drug: Look good and feel good, be physically fit, overeat without gain weight, extend life span, slow down the aging process, cure diseases, and cure cancer. Read this very interesting article.
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Can red wine help you live forever?
Turns out there's something to it.
Fortune's David Stipp recounts the amazing, real story of the scientist and startup that have a shot at making it happen.
By David Stipp, Fortune
January 19 2007: 12:54 PM EST

NEW YORK (Fortune) -- If you haven't heard of resveratrol, you're probably too young to have had the experience of gazing in the bathroom mirror in the morning and thinking, "damn."

Resveratrol is the ingredient in red wine that made headlines in November when scientists demonstrated that it kept overfed mice from gaining weight, turned them into the equivalent of Olympic marathoners, and seemed to slow down their aging process. Few medical discoveries have generated so much instant buzz - even Jay Leno riffed about it in his opening monologue.

But the key question raised by the news - whether the discoveries will lead to pharmaceutical payoffs before we're too old to care - won't be answered in the Harvard lab from which the news sprang. Instead look to a boxy, low-rise building a couple of miles away, an unprepossessing biotech hatchery that got little media attention in the wake of the resveratrol findings. This is the Cambridge home of two-year-old Sirtris Pharmaceuticals. Its stated goal is to develop medicines that have the same health-boosting effects in people that resveratrol had on mice.
But that hardly captures the company's sweeping promise: if it succeeds, its medicines may retard the onset or progression of a whole slew of age-related diseases, from diabetes to Alzheimer's to cancer. The drugs may also have an extremely provocative side effect: They might extend life span. You have to go back to the advent of antibiotics in the first half of the 20th century to find such broad therapeutic potential.

For all that to happen, Sirtris, like most biotech startups, must wend through a minefield that will take many years to traverse. And no biotech gets very far through the minefield without a kind of walking contradiction leading the way - a dreamer with feet planted firmly on the ground, a science whiz who could pass as a circus ringmaster, a riverboat gambler with a passion for minimizing risk. Three years ago one such paradox strolled into the Harvard lab that put resveratrol on the map and set in motion events that may in time radically transform the way we age: meet Christoph Westphal, Sirtris's co-founder, CEO, and dreamer-in-chief.

click link for the remainer of this article:
http://money.cnn.com/2007/01/18/maga...tune/index.htm