Racha Halawi “Identification and characterization of crude and purified extracts from the Indigenous Lebanese plant Ep using in vitro models of squamous cell carcinogenesis”, June 2006
 
Natural products have been invaluable as a basis for the development of front-line drugs. For thousands of years, medicine and natural products have been intimately coupled due to the use of traditional herbs and natural poisons. Drug discovery from medicinal plants has played an instrumental role in the treatment of cancer and, indeed, nearly all new clinical applications of plant secondary metabolites and their derivatives over the last half century have been directed towards battling cancer. Over fifty anticancer drugs are currently available for clinical use, the majority of which are either natural products or derivatives of natural products.The aim of our studies is to identify potential chemopreventive and/or chemotherapeutic extracts from the Lebanese indigenous plant E p. Following several series of extractions, our main purpose was to isolate and characterize a pure molecule from Ep plant extracts that would exhibit antitumorigenic activity, with minimal effect on normal cells. Towards this end, we used murine and human in vitro models of squamous cell carcinogenesis that consist of primary mouse and human keratinocytes (PMKs and PHKs) as representatives of normal cells, the SP1 papilloma cell line as murine benign cells, the PAM-212 and HaCAT as murine and human squamous carcinoma cell lines respectively, and the murine spindle I7 cell line.
 
Through bio-guided fractionation, we isolated a pure Ep molecule that suppressed the growth of cancerous cells. This molecule was not cytotoxic to PMKs at PHKs at concentrations up to 25 microgram/ml. This molecule suppressed the growth of cancerous cells, with the PAM212 and the HaCAT being the most sensitive. This molecule was found to induce a G2/M cell cycle arrest with no apoptosis induction. We also conducted western blot analysis so as to examine the levels of the various proteins that might be involved directly or indirectly in the pure molecule's mechanism of action. Our results further confirmed the G2/M arrest and suggested other alternatives to apoptotic cell death.

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