Downregulation of epidermal growth factor receptor expression contributes to α-TEA's proapoptotic effects in human ovarian cancer cell lines

Rrr-α -tocopherol derivative α-tea (rrr-α-tocopherol ether-linked acetic acid analog) has been shown to be a potent antitumor agent both in vivo and in vitro. in this study,we investigated the effects of -tea on the expression of epidermal growth factor receptor (egfr) family members,erbb1,2 and 3,and the role of erbb 2 and 3 in α-tea-induced apoptosis and suppression of akt,flip and survivin in the cisplatin-sensitive (a2780s) and -resistant (a2780/cp70r) human ovarian cancer cell lines. data show that α-tea's ability to induced apoptosis was associated with reduced expression of erbb1 (cisplatin-resistant cells),2 and 3 (both cell types) and reduced levels of the phosphorylated (active) form of akt; as well as,reduced levels of flip and survivin proteins in both cell types. ectopic overexpression and sirna knockdown studies showed that erbb2,erbb3,akt,flip and survivin are involved in α-tea-induce apoptosis and that -tea downregulates flip and survivin via suppression of pakt,which is mediated by erbb2 and erb3. thus,α-tea is a potent pro-apoptotic agent for both cisplatin-sensitive and α-resistant ovarian cancer cell lines in cell culture and it produces cell death,at least in part,by downregulation of members of the egfr family. © 2010 ming-chieh shun et al.