Bcl-2 overexpression inhibits tetrachlorohydroquinone-induced apoptosis in NIH3T3 cells: A possible mechanism for tumor promotion
✍ Scribed by Yu-Ping Lin; Ben-Zhan Zhu; Ming-Chen Yang; Balz Frei; Ming-Hsiung Pan; Jen-Kun Lin; Ying-Jan Wang
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 249 KB
- Volume
- 40
- Category
- Article
- ISSN
- 0899-1987
- DOI
- 10.1002/mc.20021
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
TCHQ is a major carcinogenic metabolite of the widely used wood preservative PCP. Recently, we found that TCHQ was a promoter in a mouse skin carcinogenesis model. However, the mechanism is still not clear. In this study, we showed that overexpression of Bcl‐2 effectively suppressed TCHQ‐induced apoptosis in NIH3T3 cells, as evidenced by morphological changes and DNA fragmentation. Although production of ROS contributes to TCHQ‐induced apoptosis, Bcl‐2 failed to attenuate TCHQ‐elicited increase of intracellular ROS level. In addition, overexpressed Bcl‐2 provides only partial protection against TCHQ‐induced cellular DNA damage. We also found that TCHQ induced a change in mitochondrial transmembrane potential, and that caspase‐9 and subsequent caspase‐3 can be activated during TCHQ‐induced acute apoptosis. Interestingly, TCHQ induced a significant upregulation of Bcl‐2 expression, and over‐expressed Bcl‐2 can dramatically inhibit the change of mitochondria membrane potential and activation of both caspase‐9 and ‐3. Thus, our results suggest TCHQ‐induced tumor promotion may be through a mechanism of upregulation of Bcl‐2 protein and subsequent apoptosis inhibition. © 2004 Wiley‐Liss, Inc.