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Gillian
Air
/ Sanjay
Bidichandani / Robert
Broyles Karla Rodgers / Robert Steinberg / Leon Unger / Paul Weigel |
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Transduction of apoptotic signals and characterizing the molecular mechanisms by which various agents elicit cell death in cancer cells; the use of natural products and their analogues and examining their structure:function effect(s) on specific cell death pathways in target cancer cells. It is well established that p21 inhibits cyclin-dependent kinases (Cdks) as well as several other factors. We have suggested that inhibition of Cdks by p21 is essential to inhibiting apoptosis and the induction of senescence in human colon cancer cells treated with the anti-cancer drug camptothecin. We have implicated STAT1 and/or p300 as transcriptional regulators affecting p21 expression in the presence of p53. Current and future studies will explore genetic and biochemical approaches to selectively alter a specific Cdk, STAT1, p300 and other proteins induced by bioactive chemicals in the HCT116 model human colon cancer cell sytem. This project has been developed by Dr. Zhiyong Han. Other studies focus on the use of genetically modified or isogenic clones of HCT 116 cells and their ability to propagate as xenografted tumors relative to the control parental cell. Our approach has been to study the use of various bioactive chemicals to suppress tumor progression. Also, similar efforts are aimed at using specific bioactive chemicals to prevent tumor formation and have been largely conducted by Dr. Panayotis Pantazis.
Publications: Han Z, Wei W, Dunaway S, Darnowski JW, Calabresi P, Sedivy J, Hendrickson EA, Balan K, Pantazis P, Wyche JH. Role of p21 in apoptosis and senescence of human colon cancer cells treated with camptothecin. J. Biol. Chem. 277: 17154-17160, 2002. Hu, X., Han, Z., Wyche, J.H., and Hendrickson, E.A. Helix 6 of tBid is necessary but not sufficient for mitochrondrial binding activity. Apoptosis, 8: 277-289, 2003. Chatterjee D, Yin, B., Wang Z., Roy R, Braastad C, Sun Y, Mukhopadhyay A, Aggarwal BB, Darnowski J, Pantazis P, Wyche J, Fu Z, Kitagwa Y, Keller ET, Sedivy JM, Yeung KC. RKIP sensitizes cancer cells to drug-induced apoptosis. J Biol Chem. 279: 17515-17523, 2004. Cai, Y., Wei, Q., Fang, J., Yang, L., Liu, Z., Wyche, J.H., Han, Z. The 3,4-Dihydroxyl Groups are Important for trans-Resveratrol Analogs to Exhibit Enhanced Antioxidant and Apoptotic Activities. Anticancer Res. 24: 999-1002, 2004. Wang, Y., Wang, B., Cai, Y,J., Wei, Q.,Y., Fang, J., G., Yang, L., Liu, Z-L., Balan, K., Pantazis, P., Wyche, J.H. and Han, Z. Induction of FADD-dependent apoptosis by the resveratrol analogue, 3,4,5-trihydroxy-trans-stilbene. Biochem. Pharmacol. 69: 249-254, 2005.
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