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Implication of Transcriptional Repression in Compound C-induced Apoptosis in Cancer Cells

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Journal Cell Death Dis
Date 2013 Oct 26
PMID 24157877
Citations 12
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Abstract

Compound C, a well-known inhibitor of AMP-activated protein kinase (AMPK), has been reported to induce apoptosis in some types of cells. However, the underlying mechanisms remain largely unclear. Using a DNA microarray analysis, we found that the expression of many genes was downregulated upon treatment with compound C. Importantly, compound C caused transcriptional repression with the induction of p53, a well-known marker of transcriptional stress response, in several cancer cell lines. Compound C did not induce the phosphorylation of p53 but dramatically increased the protein level of p53 similar to some other transcriptional inhibitors, including 5,6-dichloro-1-β-D-ribobenzimidazole (DRB). Consistent with previous reports, we found that compound C initiated apoptotic death of cancer cells in an AMPK-independent manner. Similar to DRB and actinomycin D (ActD), two classic transcription inhibitors, compound C not only resulted in the loss of Bcl-2 and Bcl-xl protein but also induced the phosphorylation of eukaryotic initiation factor-alpha (eIF2α) on Ser51. Hence, the phosphorylation of eIF2α might be a novel marker of transcriptional inhibition. It is noteworthy that compound C-mediated apoptosis of cancer cells is correlated with decreased expression of Bcl-2 and Bcl-xl and the phosphorylation of eIF2α on Ser51. Remarkably, compound C exhibits potent anticancer activities in vivo. Taken together, our data suggest that compound C may be an attractive candidate for anticancer drug development.

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References
1.
Chen R, Keating M, Gandhi V, Plunkett W . Transcription inhibition by flavopiridol: mechanism of chronic lymphocytic leukemia cell death. Blood. 2005; 106(7):2513-9. PMC: 1895272. DOI: 10.1182/blood-2005-04-1678. View

2.
Adams J, Cory S . The Bcl-2 protein family: arbiters of cell survival. Science. 1998; 281(5381):1322-6. DOI: 10.1126/science.281.5381.1322. View

3.
MacCallum D, Melville J, Frame S, Watt K, Anderson S, Gianella-Borradori A . Seliciclib (CYC202, R-Roscovitine) induces cell death in multiple myeloma cells by inhibition of RNA polymerase II-dependent transcription and down-regulation of Mcl-1. Cancer Res. 2005; 65(12):5399-407. DOI: 10.1158/0008-5472.CAN-05-0233. View

4.
Arima Y, Nitta M, Kuninaka S, Zhang D, Fujiwara T, Taya Y . Transcriptional blockade induces p53-dependent apoptosis associated with translocation of p53 to mitochondria. J Biol Chem. 2005; 280(19):19166-76. DOI: 10.1074/jbc.M410691200. View

5.
Radhakrishnan S, Gartel A . A novel transcriptional inhibitor induces apoptosis in tumor cells and exhibits antiangiogenic activity. Cancer Res. 2006; 66(6):3264-70. DOI: 10.1158/0008-5472.CAN-05-3940. View