Cisplatin,
a DNA damaging agent, induces apoptosis through increasing DNA fragmentation. However, identification of intrinsic resistance molecules against
Cisplatin is vital to estimate the success of
therapy. Bag-1 (Bcl-2-associated anthanogene) is one
anti-apoptotic protein involved in drug resistance impacting on therapeutic efficiency. Elevated levels of this
protein are related with increase cell proliferation rates, motility and also
cancer development. For this reason, we aimed to understand the role of Bag-1 expression in
Cisplatin- induced apoptosis in HeLa
cervix cancer cells.
Cisplatin decreased cell viability in time- and dose-dependent manner in wt and Bag-1L+HeLa cells. Although, 10 μM
Cisplatin treatment induced cell death within 24h by activating
caspases in wt cells, Bag-1L stable transfection protected cells against
Cisplatin treatment. To assess the potential protective role of Bag-1, we first checked the expression profile of interacting anti-apoptotic partners of Bag-1. We found that forced Bag-1L expression prevented
Cisplatin-induced apoptosis through acting on Mcl-1 expression, which was reduced after
Cisplatin treatment in wt HeLa cells. This mechanism was also supported by the regulation of
heat shock protein (Hsp) family members, Hsp90 and Hsp40, which were involved in the regulation Bag-1 interactome including several anti-apoptotic Bcl-2 family members and c-Raf.