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KMID : 0545120100200020428
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Journal of Microbiology and Biotechnology
2010 Volume.20 No. 2 p.428 ~ p.432
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Cell Cycle Arrest and Cytochrome C-mediated Apoptotic Induction in Human Lung Cancer A549 Cells by MCS-C2, an Analogue of Sangivamycin
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Kang Jeong-Hwa
Lee Dong-Keun
Lee Chul-Hoon
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Abstract
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In the course of our screening for novel modulators on cell cycle progression and apoptosis as anticancer drug candidates, we generated an analogue of sangivamycin, MCS-C2, designated as 4-amino-6-bromo-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide. This study was aimed to evaluate the molecular mechanisms on cell cycle arrest and apoptotic induction of MCS-C2 in human lung cancer A549 cells. To investigate the effects of MCS-C2 on cell cycle progression in A549 cells, we measured DNA content of A549 cells treated with 5 μM of HY253 using flow cytometric analysis. The flow cytometric analysis revealed an appreciable G2 phase arrest in A549 cells treated with 5 μM of MCS-C2. This MCS-C2-induced G2 phase arrest is associated with significant up-regulation of p53 and p21CIP1 in A549 cells. Furthermore, TUNEL assay was used to examine apoptotic induction in A549 cells treated with 5 μM of MCS-C2 for 48 h. In addition, the effects of MCS-C2 on apoptosis-associated proteins in A549 cells were examined using Western blot analysis. The apoptotic induction in MCS-C2-treated A549 cells is associated with cytochrome c release from mitochondria which in turn resulted in the activation of caspase-9 and -3, and the cleavage of poly(ADP-ribose) polymerase (PARP). In conclusion, based on these results, we suggest that MCS-C2 may be a potent cancer chemotherapeutic candidate for use in treating human lung cancer cells via up-regulation and activation of p53.
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KEYWORD
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Sangivamycin analogue, Cell cycle arrest, Apoptotic induction, A549 cells
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