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Mechanism of apicidin-induced cell cycle arrest and apoptosis in Ishikawa human endometrial cancer cells.
Chem Biol Interact. 2009 May 15; 179(2-3):169-77.CB

Abstract

Histone deacetylase (HDAC) inhibitors are a promising new class of anticancer agents that act by inhibiting cell proliferation and inducing apoptosis in a variety of cancer cells. Although apicidin acts as a potent HDAC inhibitor, the precise mechanism for its anti-tumor activity in human endometrial cancer cells is not completely understood. This study examined the anti-tumor effects of apicidin in Ishikawa cancer cells. The level of cell proliferation, the stage of the cell cycle, and apoptosis were measured after the apicidin treatment. Apicidin significantly inhibited the proliferation of Ishikawa cells in a dose-dependent manner. In addition, apicidin markedly up-regulated the p21(WAF1) and down-regulated the expression of cyclins (A, B1, D1, or E), and CDKs (2 or 4), which leading to cell cycle arrest. Cell cycle analysis showed that the apicidin treatment increased the proportion of cells in the G1 phase, and decreased the ratio of cells in the S phase in a dose-dependent manner. Apicidin significantly increased the sub-G1 population and the number of TUNEL positive apoptotic cells compared with the untreated control. These results were confirmed by poly-ADP ribose polymerase (PARP), an 85-kDa fragment resulting from PARP cleavage, where apicidin increased the level of PARP cleavage and caspase-3 activity in 1.0 microM apicidin-treated cells. Apicidin-induced apoptosis through caspase-3 activation was confirmed by the increase in the release of cytochrome c and the decrease in the Bax/Bcl-2 ratio. These results suggest that apicidin has anti-tumor properties on endometrial cancer cells by inducing selectively the genes related to cell cycle arrest and apoptosis.

Authors+Show Affiliations

College of Pharmacy, Pusan National University, San 30, Jangjeon-dong, Geumjung-gu, Busan 609-735, South Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19070610

Citation

Ahn, Mee Young, et al. "Mechanism of Apicidin-induced Cell Cycle Arrest and Apoptosis in Ishikawa Human Endometrial Cancer Cells." Chemico-biological Interactions, vol. 179, no. 2-3, 2009, pp. 169-77.
Ahn MY, Lee J, Na YJ, et al. Mechanism of apicidin-induced cell cycle arrest and apoptosis in Ishikawa human endometrial cancer cells. Chem Biol Interact. 2009;179(2-3):169-77.
Ahn, M. Y., Lee, J., Na, Y. J., Choi, W. S., Lee, B. M., Kang, K. W., & Kim, H. S. (2009). Mechanism of apicidin-induced cell cycle arrest and apoptosis in Ishikawa human endometrial cancer cells. Chemico-biological Interactions, 179(2-3), 169-77. https://doi.org/10.1016/j.cbi.2008.11.011
Ahn MY, et al. Mechanism of Apicidin-induced Cell Cycle Arrest and Apoptosis in Ishikawa Human Endometrial Cancer Cells. Chem Biol Interact. 2009 May 15;179(2-3):169-77. PubMed PMID: 19070610.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanism of apicidin-induced cell cycle arrest and apoptosis in Ishikawa human endometrial cancer cells. AU - Ahn,Mee Young, AU - Lee,Jaewon, AU - Na,Yong Jin, AU - Choi,Wahn Soo, AU - Lee,Byung Mu, AU - Kang,Keon Wook, AU - Kim,Hyung Sik, Y1 - 2008/11/25/ PY - 2008/08/02/received PY - 2008/11/13/revised PY - 2008/11/13/accepted PY - 2008/12/17/entrez PY - 2008/12/17/pubmed PY - 2009/5/7/medline SP - 169 EP - 77 JF - Chemico-biological interactions JO - Chem Biol Interact VL - 179 IS - 2-3 N2 - Histone deacetylase (HDAC) inhibitors are a promising new class of anticancer agents that act by inhibiting cell proliferation and inducing apoptosis in a variety of cancer cells. Although apicidin acts as a potent HDAC inhibitor, the precise mechanism for its anti-tumor activity in human endometrial cancer cells is not completely understood. This study examined the anti-tumor effects of apicidin in Ishikawa cancer cells. The level of cell proliferation, the stage of the cell cycle, and apoptosis were measured after the apicidin treatment. Apicidin significantly inhibited the proliferation of Ishikawa cells in a dose-dependent manner. In addition, apicidin markedly up-regulated the p21(WAF1) and down-regulated the expression of cyclins (A, B1, D1, or E), and CDKs (2 or 4), which leading to cell cycle arrest. Cell cycle analysis showed that the apicidin treatment increased the proportion of cells in the G1 phase, and decreased the ratio of cells in the S phase in a dose-dependent manner. Apicidin significantly increased the sub-G1 population and the number of TUNEL positive apoptotic cells compared with the untreated control. These results were confirmed by poly-ADP ribose polymerase (PARP), an 85-kDa fragment resulting from PARP cleavage, where apicidin increased the level of PARP cleavage and caspase-3 activity in 1.0 microM apicidin-treated cells. Apicidin-induced apoptosis through caspase-3 activation was confirmed by the increase in the release of cytochrome c and the decrease in the Bax/Bcl-2 ratio. These results suggest that apicidin has anti-tumor properties on endometrial cancer cells by inducing selectively the genes related to cell cycle arrest and apoptosis. SN - 1872-7786 UR - https://www.unboundmedicine.com/medline/citation/19070610/Mechanism_of_apicidin_induced_cell_cycle_arrest_and_apoptosis_in_Ishikawa_human_endometrial_cancer_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-2797(08)00629-7 DB - PRIME DP - Unbound Medicine ER -