St John's Wort: a natural plant remedy in the fight against cancer Schempp C. M et al. (2002). Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St John's wort that acts by induction of apoptosis Cancer cells thrive because in addition to engaging their proliferative machinery they also suppress intrinsic cell death pathways. Signals that in normal cells result in the triggering of apoptosis fail to do so in cancer cells, often because of the acquired mutations in apoptotic pathways. Inducing apoptosis in the treatment of cancer is therefore a promising therapeutic opportunity. Indeed, many anticancer drugs that have different modes of action have one thing in common - they kill cancer cells by triggering apoptosis. Recently, Schempp et al. demonstrated that St John's wort could join the ranks of anticancer drugs. St John's wort is a popular over-the-counter mood enhancer venerated by natural medicine enthusiasts. One of the active ingredients of St John's wort, the phloroglucin-derivative hyperforin, is a natural antibiotic that inhibits the growth of several Gram-positive bacteria. Schempp et al. now demonstrate that hyperforin also acts as a potent anticancer drug both in vitro and in vivo. The authors first evaluated the antiproliferative potential of hyperforin in 16 different human and rat cancer cell lines. In all but one case, hyperforin inhibited the growth of cancer cell lines even though many of these cell lines were resistant to other cytostatic drugs such as vincristine, paclitaxel and camptothecin. Analysis of the mode of action of hyperforin revealed that it killed cancer cells by inducing apoptosis that could be blocked by the caspase inhibitor zVAD.fmk. In fact, the treatment of cells with hyperforin resulted in the induction of caspase-3 and caspase-9 but not caspase-8, suggesting that hyperforin could have an effect on an intrinsic, mitochondria-mediated cell death pathway. Indeed, the mitochondria of hyperforin-treated cells underwent rapid loss of membrane potential. Interestingly, this loss of membrane potential could not be blocked by the pre-incubation of cells with zVAD.fmk. Instead, the treatment of cells with hyperforin induced a rapid release of cytochrome c from the mitochondria (the release of cytochrome c is essential for the initiation of mitochondria-mediated apoptosis). These results suggest that hyperforin acts by facilitating the release of cytochrome c (and perhaps other pro-apoptotic molecules) from mitochondria which in turn activates the apoptosome-associated caspase-9 and triggers the caspase cascade. Importantly, the activity of hyperforin was not limited to cultured cancer cells. When rats injected with rat mammary carcinoma cells were treated with hyperforin, it inhibited tumor growth to a similar extent as paclitaxel. Significantly, there was a complete lack of toxicity associated with the hyperforin treatment. The discovery of a new anticancer drug is often accompanied by inflated claims of its therapeutic potential. Hyperforin, however, appears to fulfill several prerequisites for a good drug candidate: (1) it seems to have activity against a wide spectrum of cancer cells, (2) it has little or no toxicity, and (3) it can be easily obtained in large quantities from St John's wort which is abundant throughout the world. Although it may be too soon to celebrate, the antitumour activity of hyperforin, and St John's wort, is quite promising and warrants further investigations. Oncogene, 21:1242-1250. BioMedNet Magazine-19 March 2002 by Martin Holcik martin@mgcheo.med.uottawa.ca Dr. David Kroll, Denver research pharmacologist Irotecan & Other Chemos w/SJW Ameican Botanical Council St John's wort Held to Higher Standards Than Conventional Commentary by Hyla Cass M.D. Medscape Wire JAMA, 2002 Cancer Letters, 7/04 Townsend Letter, 1/07 Kerry Bone, FNIMH, FNHAA Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.