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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 한국미생물생명공학회 Journal of Microbiology and Biotechnology Journal of Microbiology and Biotechnology 제20권 제2호
- 발행연도
- 2010.1
- 수록면
- 433 - 437 (5page)
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In the course of screening for novel modulators of cell cycle progression and apoptosis as anticancer drug candidates,we generated an analog of sangivamycin, MCS-C2, which was elucidated as 4-amino-6-bromo-7-cyclopentyl-7Hpyrrolo[2,3-d]pyrimidine-5-carboxamide. In the present study, we evaluated the molecular mechanisms of MCSC2-induced cell cycle arrest and apoptosis in A549 human lung cancer cells. To investigate the effects of MCS-C2 on cell cycle progression in A549 cells, we measured the DNA content of A549 cells treated with 5 μM MCS-C2 using flow cytometry. The analysis revealed an appreciable G2phase arrest in treated cells. This event was associated with significant upregulation of p53 and p21Cip1. In addition,the TUNEL assay was used to examine apoptotic induction in treated cells, and the effects of MCS-C2 on the expression of apoptosis-associated proteins were examined by Western blot. Apoptotic induction in MCS-C2-treated A549 cells was 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). Based on these results, we conclude that MCS-C2 is a candidate therapeutic agent for the treatment of human lung cancer via upregulation and activation of p53.
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참고문헌 (16)
참고문헌 신청
Canman, C. E / 1998 / Activation of the ATM kinase by ionizing radiation and phosphorylation of p53 / Science 281 : 1677 ~ 1679
Harper, J. W / 1993 / The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases / Cell 75 : 805 ~ 816
KIM, MIN KYOUNG / 2007 / Discovery of Cyclin-dependent Kinase Inhibitor, CR229, Using Structurebased Drug Screening / Journal of Microbiology and Biotechnology 17 (10) : 1712
Kim, M. K / 2005 / Induction of apoptosis in human leukemia cells by MCS-C2 via caspase-dependent Bid cleavage and cytochrome c release / Cancer Lett 223 : 239 ~ 247
Kim, M. K / 2007 / a novel derivative of beta-carbolin-1-one, induces cell cycle arrest and apoptosis in HeLa cells via p53 activation / Cancer Sci 98 : 1402 ~ 1407
Harper, J. W / 1993 / The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases / Cell 75 : 805 ~ 816
KIM, MIN KYOUNG / 2007 / Discovery of Cyclin-dependent Kinase Inhibitor, CR229, Using Structurebased Drug Screening / Journal of Microbiology and Biotechnology 17 (10) : 1712
Kim, M. K / 2005 / Induction of apoptosis in human leukemia cells by MCS-C2 via caspase-dependent Bid cleavage and cytochrome c release / Cancer Lett 223 : 239 ~ 247
Kim, M. K / 2007 / a novel derivative of beta-carbolin-1-one, induces cell cycle arrest and apoptosis in HeLa cells via p53 activation / Cancer Sci 98 : 1402 ~ 1407
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