Bag-1L is a stress-withstand molecule prevents the downregulation of Mcl-1 and c-Raf under control of heat shock proteins in cisplatin treated HeLa cervix cancer cells.

Pelin Ozfiliz,Ajda Coker-Gurkan,Narcin Palavan-Unsal,Pinar Obakan,Tugce Nur Eralp,Gizem Dinler-Doganay,Elif Damla Arisan

doi:10.7314/apjcp.2014.15.11.4475

Pelin Ozfiliz, Ajda Coker-Gurkan + Show 5 more

Open Access

https://doi.org/10.7314/apjcp.2014.15.11.4475

Copy DOI

Abstract

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.

Highlights

Cervical cancer affects the women worldwide and it is the second most common cancer remaining a major health problem because of high oncogenic human papilloma virus (HPV) infection rates (Packham et al, 1997)
Recent studies suggested that silencing of Bag-1 enhanced the sensitivity against Cisplatin treatment through modulating Bcl-2 family members in A549 and L9981 lung cancer cell lines (Liu et al, 2010)
It is hypothesized that Bag-1 binds to heat shock protein (Hsp)/Hsc70-substrate complexes to regulate the potential substrates of this complex such as Bcl-2, Raf, NHRs (Wang et al, 1996; Wang and Reed 1998; Dobbyn et al, 2008)

Summary

Introduction

Cervical cancer affects the women worldwide and it is the second most common cancer remaining a major health problem because of high oncogenic human papilloma virus (HPV) infection rates (Packham et al, 1997). 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 cancer development. For this reason, we aimed to understand the role of Bag-1 expression in Cisplatininduced apoptosis in HeLa cervix cancer cells. 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 supported by the regulation of heat shock protein (Hsp) family members, Hsp and Hsp, which were involved in the regulation Bag-1 interactome including several anti-apoptotic Bcl-2 family members and c-Raf

Objectives

Methods

Results

Conclusion