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Chaoqun Zheng


chaoqun-zheng@uiowa.edu
Mentor: Raymond Hohl, M.D./Ph.D.
Lab Room: 5219 MERF
Lab Phone: 319-335-8272

The molecular mechanisms of anti-cancer activity for schweinfurthins

Schweinfurthins represent a novel class of anti-cancer natural compounds isolated from an African plant Macaranga schweinfurthii. The schweinfurthins show selective and unique cytotoxicity profile in the NCI 60 human cancer cell lines with an average GI50 value less than 0.5 μM. The central nervous system, leukemia and renal cancer panels are among the most sensitive to schweinfurthins whereas the lung cancer A549 cells are resistant. The pattern of schweinfurthins activity shows no correlation with any other anti-cancer drugs in clinic use suggesting that schweinfurthins act at a novel cellular target or through a previously unrecognized mechanism. To elucidate the molecular basis of schweinfurthin-induced cell death, I wish to identify the molecular target of schweinfurthins that is responsible for schweinfurthins anti-cancer activity. Also, I would like to investigate the determinants of cellular sensitivity to schweinfurthins by a systematic genetic screen. Previous studies have shown that the inappropriate activation of the Hedgehog signaling is required for tumor development. Interestingly, I found that schweinfurthins inhibit the Hedgehog signaling pathway in SF-295 cells and synergize with cyclopamine, a Hedgehog signaling antagonist. I will further map the action of schweinfurthins in the Hedgehog signaling pathway. A better understanding of the mechanisms of schweinfurthins action will help to facilitate the clinical application of schweinfurthins in the future. In addition, this study may reveal a novel molecular target for the treatment of cancer.