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Bid-overexpression regulates proliferation and phosphorylation of Akt and MAPKs in response to etoposide-induced DNA damage in hepatocellular carcinoma cells
| Content Provider | Semantic Scholar |
|---|---|
| Author | Li, Yuanyue Dai, Congjie Li, Juan Jenny Wang, Weiwei Song, Gang |
| Copyright Year | 2012 |
| Abstract | BACKGROUND Growing evidence supports BH3-interacting domain death agonist (Bid) playing a dual role in DNA damage response. However, the effects of Bid on hepatocellular carcinoma (HCC) cell proliferation in response to etoposide-induced DNA damage have not been sufficiently investigated. METHODS Using a stable Bid-overexpression HCC cell line, Bid/PLC/PRF/5, overexpression of Bid promoted loss of viability in response to etoposide-induced DNA damage. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]- and BrdU (5'-bromo-2'-deoxyuridine)-labeling assays revealed that etoposide-inhibited HCC cells grew in concentration-and time-dependent manners. The phosphorylations of Akt and mitogen-activated protein kinases (MAPKs) in response to etoposide-induced DNA damage were analyzed by Western blotting. RESULTS The survival rates of 100 μM etoposide on the cells with control vector and Bid/PLC/PRF/5 at 48 hours amounted to 71% ± 0.75% and 59% ± 0.60% with MTT assay, and similar results of 85% ± 0.08% and 63% ± 0.14% with BrdU-labeling assay respectively. Moreover, overexpression of Bid sensitized the cells to apoptosis at a high dose of etoposide (causing irreparable damage). However, it had little effect on the proliferation at a low dose of etoposide (repairable damage). Furthermore, the phosphorylation status of Akt and MAPKs were investigated. Overexpression of Bid suppressed the activation of Akt with respect to etoposide-induced DNA damage. Similar to Akt, the levels of phosphorylated p38 and phosphorylated c-Jun were attenuated by Bid-overexpression. On the contrary, the level of phosphorylated ERK1/2 was sustained at a high level, especially in Bid/PLC/PRF/5 cells. CONCLUSION Taken together, these results suggest that overexpression of Bid suppressed the activation of Akt, p38, and c-Jun, and promoted the activation of ERK1/2 induced by etoposide, suggesting that the promotion of ERK1/2 activation may have a negative effect on Bid-mediated HCC DNA damage induced by etoposide. |
| Starting Page | 279 |
| Ending Page | 286 |
| Page Count | 8 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://www.dovepress.com/getfile.php?fileID=14257 |
| PubMed reference number | 23093908 |
| Alternate Webpage(s) | https://doi.org/10.2147/OTT.S36087 |
| DOI | 10.2147/ott.s36087 |
| Journal | OncoTargets and therapy |
| Volume Number | 5 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Apoptosis Bromodeoxyuridine Cell Proliferation Dual Fifty Nine Liver carcinoma Mitogen-Activated Protein Kinases Mitogens Phosphorylation Proto-Oncogene Proteins c-akt Western Blotting monooxyethylene trimethylolpropane tristearate positive regulation of response to G1 DNA damage checkpoint signaling response to etoposide |
| Content Type | Text |
| Resource Type | Article |
