In vitro and in vivo anticancer action of @entity485 -NO, a novel nitric oxide-derivative of the protease inhibitor @entity485 , on hormone resistant XXXX cells.

@entity263 @entity485 @entity2205 @entity645 @entity3049 @entity876 @entity19767 @entity65340
The NO-derivative of the @entity645 protease inhibitor @entity485 ( @entity65340 ) is a nontoxic variant of the parental drug with enhanced anticancer activity on several cell lines. However, it is still unclear whether the @entity876 status of the target cell might influence the sensitivity to @entity65340 . In this study we evaluated the in vitro and in vivo activity of @entity65340 on the @entity876 - @entity263 PC-3 cells. We demonstrate that the absence of functional @entity876 is not essential for the capacity of @entity65340 to reduce @entity263 cell growth. In contrast to its previously described cytostatic action in B16 and C6 cell lines, @entity65340 exerted cytotoxic effects in PC-3 cells leading to dominant induction of apoptosis and enhanced production of proapoptotic Bim. In addition, differently from @entity485 , @entity65340 restored @entity2205 sensitivity that was correlated with increased expression of @entity3049 independent from ROS/RNS production and @entity19767 repression. NF-kB activation may be responsible of the @entity65340 induced @entity3049 expression. Moreover, @entity65340 but not @entity485 , exerted synergistic activity with conventional cytostatic therapy. In agreement with these in vitro studies, @entity65340 inhibited the in vivo growth of PC-3 cells xenotransplants to a greater extent than the parental compound. Taken together, these data indicate that @entity65340 possesses powerful and suitable in vitro and in vivo chemotherapeutic potential to be further studied as a novel drug for the treatment of @entity263 in the clinical setting.
