Oncogenic H-Ras, FK228, and exogenous H2O2 cooperatively activated the erk pathway in selective induction of human urinary bladder cancer j82 cell death
✍ Scribed by Shambhunath Choudhary; Kwo-Kwang Abraham Wang; Hwa-Chain Robert Wang
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 179 KB
- Volume
- 50
- Category
- Article
- ISSN
- 0899-1987
- DOI
- 10.1002/mc.20708
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✦ Synopsis
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.