Combination of erlotinib and EGCG induces apoptosis of head and neck cancers through posttranscriptional regulation of Bim and Bcl-2

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 b...
Source: Apoptosis - Category: Molecular Biology Source Type: research

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Authors: Hu D, Zhang B, Yu M, Shi W, Zhang L Abstract Colorectal cancer is one of the commoner digestive tract malignant tumor types, and its incidence and mortality rate are high. Accumulating evidence indicates that long‑chain non‑coding RNAs (lncRNAs) and protein‑coding RNAs interact with each other by competing with the same micro(mi)RNA response element (MREs) and serve an important role in the regulation of gene expression in a variety of tumor types. However, the regulatory mechanism and prognostic role of lncRNA‑mediated competing endogenous (ce)RNA networks in colon cancer have yet to be elucidated...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
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Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
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Source: Trends in Molecular Medicine - Category: Molecular Biology Authors: Tags: Trends Mol Med Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
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Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
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Source: FEBS Letters - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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