Flavopiridol, a cyclin dependent kinase (CDK) inhibitor, induces apoptosis by regulating Bcl-x in oral cancer cells

被引：28

作者：

Mihara, M ^{[1
]}

Shintani, S ^{[1
]}

Nakashiro, K ^{[1
]}

Hamakawa, H ^{[1
]}

机构：

[1] Ehime Univ, Sch Med, Dept Oral & Maxillofacial Surg, Shigenobu, Ehime 7910295, Japan

来源：

ORAL ONCOLOGY | 2003年 / 39卷 / 01期

关键词：

CDK inhibitor; oral cancer; apoptosis;

D O I：

10.1016/S1368-8375(02)00019-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Flavopiridol is a synthetic flavone that inhibits tumor growth by suppressing cyclin-dependent kinases (CDKs). We have investigated effects of flavopiridol in oral squamous cell carcinoma (OSCC). Flavopiridol was found to inhibit the growth of OSCC cells in a time- and dose-dependent manner. Induction of apoptosis was observed in all cells showing accumulated cells with sub-G, DNA contents, DNA fragmentations, and PARP cleavages. While Bcl-2 and Bax expression did not change, Bcl-X-L was down regulated and Bcl-xs was up-regulated after being exposed to flavopiridol. Flavopiridol treatments also resulted in remarkable reductions of cyclin A, cyclin B, and cyclin D1 expressions. We also found that expression levels of CDK activation kinase and CDC25C were reduced, and p34 inactive form CDK2 were up-regulated. Our data indicate that flavopiridol has growth inhibition activities against OSCC. Flavopiridol not only inhibits CDKs directly, but it also inhibits the CDKs activation pathway and activates the Bcl-x apoptotic pathway. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：49 / 55

页数：7

共 50 条

[41] The farnesyltransferase inhibitor, FPT inhibitor III upregulates Bax and Bcl-xs expression and induces apoptosis in human ovarian cancer cells [J].

Hung, WC ;

Chaung, LY .

INTERNATIONAL JOURNAL OF ONCOLOGY, 1998, 12 (01) :137-140

[42] Caspase-dependent apoptosis of COS-7 cells induced by Bax overexpression: differential effects of Bcl-2 and Bcl-x(L) on Bax-induced caspase activation and apoptosis [J].

Kitanaka, C ;

Namiki, T ;

Noguchi, K ;

Mochizuki, T ;

Kagaya, S ;

Chi, S ;

Hayashi, A ;

Asai, A ;

Tsujimoto, Y ;

Kuchino, Y .

ONCOGENE, 1997, 15 (15) :1763-1772

[43] Alsterpaullone, a novel cyclin-dependent kinase inhibitor, induces apoptosis by activation of caspase-9 due to perturbation in mitochondrial membrane potential [J].

Lahusen, T ;

De Siervi, A ;

Kunick, C ;

Senderowicz, AM .

MOLECULAR CARCINOGENESIS, 2003, 36 (04) :183-194

[44] Cyclin dependent kinase 5 (Cdk5) mediated inhibition of the MAP kinase pathway results in CREB down regulation and apoptosis in PC12 cells [J].

Sharma, Monica ;

Hanchate, Naresh Kumar ;

Tyagi, Rakesh K. ;

Sharma, Pushkar .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2007, 358 (02) :379-384

[45] Downregulation of XIAP and induction of apoptosis by the synthetic cyclin-dependent kinase inhibitor GW8510 in non-small cell lung cancer cells [J].

Dong, FQ ;

Guo, W ;

Zhang, LD ;

Wu, SH ;

Teraishi, F ;

Davis, JJ ;

Fang, BL .

CANCER BIOLOGY & THERAPY, 2006, 5 (02) :165-170

[46] Cyclin-dependent kinase inhibitors, roscovitine and purvalanol, induce apoptosis and autophagy related to unfolded protein response in HeLa cervical cancer cells [J].

Ozfiliz-Kilbas, Pelin ;

Sarikaya, Bahar ;

Obakan-Yerlikaya, Pinar ;

Coker-Gurkan, Ajda ;

Arisan, Elif Damla ;

Temizci, Benan ;

Palavan-Unsal, Narcin .

MOLECULAR BIOLOGY REPORTS, 2018, 45 (05) :815-828

[47] Adenosine dialdehyde, a methyltransferase inhibitor, induces colorectal cancer cells apoptosis by regulating PIMT:p53 interaction [J].

Chatterjee, Tanaya ;

Guha, Deblina ;

Dhar, Jesmita ;

Saha, Taniya ;

Paul, Debamita ;

Sa, Gaurisankar ;

Chakrabarti, Pinak .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2023, 684

[48] CDK inhibitor targets: a hit or miss proposition? Cyclin-dependent kinase inhibitors kill tumor cells by downregulation of anti-apoptotic proteins [J].

Dai, Y ;

Grant, S .

CANCER BIOLOGY & THERAPY, 2006, 5 (02) :171-173

[49] Inhibition of polyamine oxidase prevented cyclin-dependent kinase inhibitor-induced apoptosis in HCT 116 colon carcinoma cells [J].

Ajda Çoker Gürkan ;

Elif Damla Arısan ;

Pınar Obakan ;

Narçin Palavan-Ünsal .

Apoptosis, 2013, 18 :1536-1547

[50] Piperine Induces Apoptosis and Autophagy in HSC-3 Human Oral Cancer Cells by Regulating PI3K Signaling Pathway [J].

Han, Eun-Ji ;

Choi, Eun-Young ;

Jeon, Su-Ji ;

Lee, Sang-Woo ;

Moon, Jun-Mo ;

Jung, Soo-Hyun ;

Jung, Ji-Youn .

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2023, 24 (18)

← 1 2 3 4 5 →