Hyperproliferation of the premalignant epithelium is critical for colonic carcinogenesis; however the mechanisms remain largely unexplored. We report herein that prior to occurrence of neoplastic lesions in the azoxymethane-rat model of colon carcinogenesis; the tumor suppressor gene C-terminal Src kinase (Csk) was down-regulated with a concomitant increase in Src activity. Furthermore, pharmacological or genetic (RNA interference) inhibition of Csk resulted in increased proliferation in colon cancer cell lines through the mitogen-activated protein kinase dependent pathway. Thus, we demonstrate, for the first time, that Csk suppression is an important early event in colorectal cancer pathogenesis.
A b s t r a c t A r t i c l e I n f oThe present review describes the biological activities of synthetic anabolic halogenated (F, Cl, Br and I) steroids. About sixty biologically active halogenated steroids have shown confirmed anti-inflammatory, estrogenic, anabolic, gynecological disorders, anti-arthritic, antineoplastic, and other activities. The structures and reported and predicted activities of halogenated steroids are available. With the computer programme PASS and based on structure-activity relationships (SAR), some additional activities are also predicted, which point towards new possible applications of these lipids. This review emphasizes the role of halogenated steroids as an important source and potential leads for drug discovery and they are of great interest to chemists, physicians, biologists, pharmacologists and the pharmaceutical industry.
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