Dihydromyricetin suppresses the proliferation of hepatocellular carcinoma cells by inducing G2/M arrest through the Chk1/Chk2/Cdc25C pathway

被引：75

作者：

Huang, Haili ^{[1
]}

Hu, Min ^{[1
]}

Zhao, Rui ^{[3
]}

Li, Peng ^{[2
]}

Li, Mingyi ^{[1
]}

机构：

[1] Guangdong Med Coll, Affiliated Hosp, Lab Hepatobiliary Surg, Zhanjiang 524001, Guangdong, Peoples R China

[2] Guangdong Med Coll, Affiliated Hosp, Clin Res Ctr, Zhanjiang 524001, Guangdong, Peoples R China

[3] Southern Med Univ, Inst Gene Engn, Guangzhou 510515, Guangdong, Peoples R China

来源：

ONCOLOGY REPORTS | 2013年 / 30卷 / 05期

关键词：

dihydromyricetin; hepatocellular carcinoma; G2/M arrest; cdk1/cylin B1 complex; 14-3-3; PROTEIN-BINDING; DNA-DAMAGE; PHASE ARREST; HUMAN CDC25C; CYCLIN B1; PHOSPHORYLATION; P53; CHK2; ACTIVATION; KINASE;

D O I：

10.3892/or.2013.2705

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The aim of the present study was to evaluate the antitumor mechanism of dihydromyricetin (DHM). Results showed that DHM significantly inhibited cell viability of HepG2 and Hep3B cells in a dose-dependent manner. DHM induced G2/M cell-cycle arrest in HepG2 and Hep3B cells by altering the expression of cell cycle proteins such as cyclin A, cyclin B1, Cdk1, p53, Cdc25c, p-Cdc25c Chk1 and Chk, which are critical for G2/M transition. Knockdown of p53 and Chk1 in HepG2 cells did not affect G2/M phase arrest caused by DHM. Furthermore, G2/M arrest induced by DHM can be disrupted by Chk2 siRNA. These findings indicate that DHM inhibits the growth of hepatocellular carcinoma (HCC) cells via G2/M phase cell cycle arrest through Chk1/Chk2/Cdc25C pathway. The present study identified effects of DHM in G2/M phase arrest in HCC and described detailed mechanisms of G2/M phase arrest by this agent, which may contribute to its overall cancer preventive efficacy in HCC.

引用

页码：2467 / 2475

页数：9

共 40 条

[1] Checkpoint kinase 2 (Chk2) monomers or dimers phosphorylate Cdc25C after DNA damage regardless of threonine 68 phosphorylation [J].

Ahn, J ;

Prives, C .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (50) :48418-48426

[2] Enhanced phosphorylation of p53 by ATN in response to DNA damage [J].

Banin, S ;

Moyal, L ;

Shieh, SY ;

Taya, Y ;

Anderson, CW ;

Chessa, L ;

Smorodinsky, NI ;

Prives, C ;

Reiss, Y ;

Shiloh, Y ;

Ziv, Y .

SCIENCE, 1998, 281 (5383) :1674-1677

[3] Phosphorylation of Xenopus Cdc25C at Ser285 Interferes with Ability to Activate a DNA Damage Replication Checkpoint in Pre-Midblastula Embryos [J].

Bulavin, Dmitry V. ;

Demidenko, Zoya N. ;

Phillips, Crissy ;

Moody, Sally A. ;

Fornace, Albert J., Jr. .

CELL CYCLE, 2003, 2 (03) :263-266

[4] Activation of the ATM kinase by ionizing radiation and phosphorylation of p53 [J].

Canman, CE ;

Lim, DS ;

Cimprich, KA ;

Taya, Y ;

Tamai, K ;

Sakaguchi, K ;

Appella, E ;

Kastan, MB ;

Siliciano, JD .

SCIENCE, 1998, 281 (5383) :1677-1679

[5] p53-independent induction of p21 (WAF1/CIP1), reduction of cyclin B1 and G2/M arrest by the isoflavone genistein in human prostate carcinoma cells [J].

Choi, YH ;

Lee, WH ;

Park, KY ;

Zhang, LJ .

JAPANESE JOURNAL OF CANCER RESEARCH, 2000, 91 (02) :164-173

[6]

Dalal SN, 1999, MOL CELL BIOL, V19, P4465

[7] CDC25 PHOSPHATASES AS POTENTIAL HUMAN ONCOGENES [J].

GALAKTIONOV, K ;

LEE, AK ;

ECKSTEIN, J ;

DRAETTA, G ;

MECKLER, J ;

LODA, M ;

BEACH, D .

SCIENCE, 1995, 269 (5230) :1575-1577

[8] Cdc25-dependent activation of cyclin A/cdk2 is blocked in G2 phase arrested cells independently of ATM/ATR [J].

Goldstone, S ;

Pavey, S ;

Forrest, A ;

Sinnamon, J ;

Gabrielli, B .

ONCOGENE, 2001, 20 (08) :921-932

[9] Localization of human Cdc25C is regulated both by nuclear export and 14-3-3 protein binding [J].

Graves, PR ;

Lovly, CM ;

Uy, GL ;

Piwnica-Worms, H .

ONCOGENE, 2001, 20 (15) :1839-1851

[10]

He Guixia, 2003, Zhong Yao Cai, V26, P338

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