The Role of Cdk5 in Retinoic Acid-Induced Apoptosis of Cervical Cancer Cell Line

Hung-Shou Kuo; Fu-Ning Hsu; Ming-Ching Chiang; Shuen-Chi You; Mei-Chih Chen; Ming-Jae Lo; Ho Lin

doi:10.4077/CJP.2009.AMG067

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医药卫生 > 基础医学

DOI： 10.4077/CJP

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The Role of Cdk5 in Retinoic Acid-Induced Apoptosis of Cervical Cancer Cell Line

Hung-Shou Kuo ； Fu-Ning Hsu ； Ming-Ching Chiang ； Shuen-Chi You ； Mei-Chih Chen ； Ming-Jae Lo ； Ho Lin

The Chinese Journal of Physiology ； 52 卷 1 期 (2009 / 02 / 01) ， P23 - 30

英文 DOI： 10.4077/CJP.2009.AMG067

retinoic acid ； apoptosis ； Cdk5 ； p35 ； HeLa cells

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摘要 │ 参考文献 (26) │ 被引用文献 (3) │ 国际计量

并列摘要〈TOP〉

Cdk5 is a small serine/threonine protein kinase which belongs to Cdk family. Unlike other Cdk members, so far Cdk5 is known to be irrelevant in cell cycle. Cdk5 kinase activity is regulated by binding with its activator, p35. Our previous results indicate that Cdk5 and p35 are involved in drugs-induced apoptosis of prostate cancer cells. Retinoic acid (RA) is one of the vitamin A-related compounds. Because of its potency on biological functions, it has been widely studied in its novel actions including the ability to inhibit cancer cell growth and to induce apoptosis. Here, we report that RA treatment decreased the growth of human cervical cancer cell line, HeLa, and Cdk5 contributed to this effect. The involvement of Cdk5 in RA-reduced cell survival was performed by treatments of Cdk5 inhibitor and siRNA. We further identified that RA-induced growth inhibition was partly correlated to Cdk5 activityrelated apoptosis by detecting cell cycle distribution of sub G1 phase and the signals of Annexin V staining. In addition, our results also indicated that Cdk5 activity was involved in RA-induced HeLa apoptosis by detecting cleavages of caspase-3 and its substrate, PARP (poly (ADP-ribose) polymerases) Interestingly, the nuclear localizations of Cdk5 and p35 proteins were increased by RA treatment, which, again, suggests the involvement of Cdk5 and p35 in RA-induced apoptotic effects. In conclusion, we provide evidence to suggest that Cdk5 and p35 might play important roles in RA-induced HeLa apoptosis.

参考文献 ( 26 ) 〈TOP〉

Ahuja, H.S.,Szanto, A.,Nagy, L.,Davies, P.J.(2003).The retinoid X receptor and its ligands: versatile regulators of metabolic function, cell differentiation and cell death.J. Biol. Regul. Homeost. Agents,17,29-45.
Alvarez, A.,Munoz, J.P.,Maccioni, R.B.(2001).A Cdk5-p35 stable complex is involved in the β-amyloid-induced deregulation of Cdk5 activity in hippocampal neurons.Exp. Cell Res.,264,266-274.
Brown, A.M.,Riddoch, F.C.,Robson, A.,Redfern, C.P.,Cheek, T.R.(2005).Mechanistic and functional changes in Ca2+ entry after retinoic acid-induced differentiation of neuroblastoma cells.Biochem. J.,388,941-948.
Chergui, K.,Svenningsson, P.,Greengard, P.(2004).Cyclin-dependent kinase 5 regulates dopaminergic and glutamatergic transmission in the striatum.Proc. Natl. Acad. Sci. U.S.A.,101,2191-2196.
Chomienne, C.,Fenaux, P.,Degos, L.(1996).Retinoid differentiation therapy in promyelocytic leukemia.FASEB J.,10,1025-1030.

被引用文献 ( 3 ) 〈TOP〉

Tang, Tswen-Kei,Su, Mei-Ju,Lin, Chia-Wen,Liao, May-Hua,Chiu, Shih-Che(2015).Induction of Survivin Inhibition, G2/M Cell Cycle Arrest and Autophagic on Cell Death in Human Malignant Glioblastoma Cells.中国生理学杂志,58(2),95-103.
Wu, Hsi-Chin,Tsai, Fu-Jenn,Tsai, Chang-Hai,Ting, Wei-Jen,Lin, Tien-Huang,Lee, Shang-Seu,Kuo, Sheng-Chu,Huang, Chih-Yang,Chien, Wen-Shin,Chen, Wen-Chi(2014).Induction of Apoptosis in Human DU145 Prostate Cancer Cells by KHC-4 Treatment.中国生理学杂志,57(2),99-104.
(2013).Effects of 3,5,3'-Triiodothyronine (T3) and Follicle Stimulating Hormone on Apoptosis and Proliferation of Rat Ovarian Granulosa Cells.中国生理学杂志,56(5),298-305.

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