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Oncogenic H‐Ras, FK228, and exogenous H 2 O 2 cooperatively activated the erk pathway in selective induction of human urinary bladder cancer j82 cell death
Author(s) -
Choudhary Shambhunath,
Wang KwoKwang Abraham,
Wang HwaChain Robert
Publication year - 2011
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20708
Subject(s) - biology , mapk/erk pathway , cancer research , cancer , cancer cell , microbiology and biotechnology , signal transduction , genetics
More than 35% of human urinary bladder cancers involve oncogenic H‐Ras activation. The goal of this study was to investigate the role of the ERK pathway in mediating apoptotic signals induced by oncogenic H‐Ras, FK228 treatment, and exogenous H 2 O 2 treatment to increase Nox‐1 elevation, leading to production of intracellular reactive oxygen species (ROS) for inducing apoptosis in human bladder cancer J82 cells. Our study revealed that FK228 combined with exogenous H 2 O 2 cooperatively induced activation of Mek1/2 and Erk1/2 to increase Nox‐1 elevation, intracellular ROS production, caspase activation, and cell death. Expression of oncogenic H‐Ras significantly increased these FK228‐ and exogenous H 2 O 2 ‐induced effects. Oncogenic H‐Ras‐increased cell susceptibility to FK228 could be alternately achieved by additional treatment with exogenous H 2 O 2 . Hence, combined use of FK228 with ROS‐generating agents may apply to therapeutic strategies to preferentially kill malignant cells with or without oncogenic H‐Ras activation. ©2010 Wiley‐Liss, Inc.