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| Content Provider | Springer Nature Link |
|---|---|
| Author | Haque, Abedul Rahman, Mohammad Aminur Chen, Zhuo Georgia Saba, Nabil F. Khuri, Fadlo R. Shin, Dong M. Ruhul Amin, A. R. M. |
| Copyright Year | 2015 |
| Abstract | Combinatorial approaches using two or more compounds are gaining increasing attention for cancer therapy. We have previously reported that the combination of the EGFR-TKI erlotinib and epigallocatechin-3-gallate (EGCG) exhibited synergistic chemopreventive effects in head and neck cancers by inducing the expression of Bim, p21, p27, and by inhibiting the phosphorylation of ERK and AKT and expression of Bcl-2. In the current study, we further investigated the mechanism of regulation of Bim, Bcl-2, p21 and p27, and their role in apoptosis. shRNA-mediated silencing of Bim significantly inhibited apoptosis induced by the combination of erlotinib and EGCG (p = 0.005). On the other hand, overexpression of Bcl-2 markedly protected cells from apoptosis (p = 0.003), whereas overexpression of constitutively active AKT only minimally protected cells from apoptosis induced by the combination of the two compounds. Analysis of mRNA expression by RT-PCR revealed that erlotinib, EGCG and their combination had no significant effects on the mRNA expression of Bim, p21, p27 or Bcl-2 suggesting the post-transcriptional regulation of these molecules. Furthermore, we found that erlotinib or the combination of EGCG and erlotinib inhibited the phosphorylation of Bim and stabilized Bim after inhibition of protein translation by cycloheximide. Taken together, our results strongly suggest that the combination of erlotinib and EGCG induces apoptosis of SCCHN cells by regulating Bim and Bcl-2 at the posttranscriptional level. |
| Starting Page | 986 |
| Ending Page | 995 |
| Page Count | 10 |
| File Format | |
| ISSN | 13608185 |
| Journal | Apoptosis |
| Volume Number | 20 |
| Issue Number | 7 |
| e-ISSN | 1573675X |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2015-04-10 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Erlotinib Epigallocatechin-3-gallate Bim Apoptosis SCCHN Cancer Research Cell Biology Oncology Biochemistry Virology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmaceutical Science Biochemistry (medical) Cell Biology Clinical Biochemistry Cancer Research Pharmacology |
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