Diosgenin, a naturally occurring steroid, suppresses fatty acid synthase expression in HER2-overexpressing breast cancer cells through modulating Akt, mTOR and JNK phosphorylation

被引：120

作者：

Chiang, Chun-Te ^{[1
]}

Way, Tzong-Der ^{[2
]}

Tsai, Shang-Jie ^{[2
]}

Lin, Jen-Kun ^{[1
,2
]}

机构：

[1] Natl Taiwan Univ, Coll Med, Inst Biochem & Mol Biol, Taipei 100, Taiwan

[2] China Med Univ, Coll Life Sci, Sch Biol Sci & Technol, Taichung, Taiwan

来源：

FEBS LETTERS | 2007年 / 581卷 / 30期

关键词：

FAS; HER2; diosgenin; Akt; mTOR; JNK;

D O I：

10.1016/j.febslet.2007.11.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Fatty acid synthase (FAS) expression is markedly elevated in HER2-overexpressing breast cancer cells. In this study, diosgenin, a plant-derived steroid, was found to be effective in suppressing FAS expression in HER2-overexpressing breast cancer cells. Diosgenin preferentially inhibited proliferation and induced apoptosis in HER2-overexpressing cancer cells. Furthermore, diosgenin inhibited the phosphorylation of Akt and mTOR, and enhanced phosphorylation of JNK. The use of pharmacological inhibitors revealed that the modulation of Akt, mTOR and JNK phosphorylation was required for diosgenin-induced FAS suppression. Finally, we showed that diosgenin could enhance paclitaxel-induced cytotoxicity in HER2-overexpressing cancer cells. These results suggested that diosgenin has the potential to advance as chemopreventive or chemotherapeutic agent for cancers that overexpress HER2. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：5735 / 5742

页数：8

共 41 条

[21] Targeting mammalian target of rapamycin synergistically enhances chemotherapy-induced cytotoxicity in breast cancer cells [J].

Mondesire, WH ;

Jian, WG ;

Zhang, HX ;

Ensor, J ;

Hung, MC ;

Mills, GB ;

Meric-Bernstam, F .

CLINICAL CANCER RESEARCH, 2004, 10 (20) :7031-7042

[22]

Peeters PHM, 2003, BREAST CANCER RES TR, V77, P171, DOI 10.1023/A:1021381101632

[23]

Pizer ES, 1996, CANCER RES, V56, P2745

[24]

Raju J, 2004, CANCER EPIDEM BIOMAR, V13, P1392

[25] FRACTIONATION OF LIVERS FOLLOWING DIOSGENIN TREATMENT TO ELEVATE BILIARY CHOLESTEROL [J].

ROMAN, ID ;

THEWLES, A ;

COLEMAN, R .

BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM, 1995, 1255 (01) :77-81

[26] Mechanisms of cancer chemoprevention by soy isoflavone genistein [J].

Sarkar, FH ;

Li, YW .

CANCER AND METASTASIS REVIEWS, 2002, 21 (3-4) :265-280

[27] Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, IκB kinase activation and NF-κB-regulated gene expression [J].

Shishodia, S ;

Aggarwal, BB .

ONCOGENE, 2006, 25 (10) :1463-1473

[28] STUDIES OF THE HER-2/NEU PROTO-ONCOGENE IN HUMAN-BREAST AND OVARIAN-CANCER [J].

SLAMON, DJ ;

GODOLPHIN, W ;

JONES, LA ;

HOLT, JA ;

WONG, SG ;

KEITH, DE ;

LEVIN, WJ ;

STUART, SG ;

UDOVE, J ;

ULLRICH, A ;

PRESS, MF .

SCIENCE, 1989, 244 (4905) :707-712

[29] Activation of c-Jun N-terminal kinase 1 and caspase 3 in the tamoxifen-induced apoptosis of rat glioma cells [J].

Tseng, SH ;

Wang, CH ;

Lin, SM ;

Chen, CK ;

Huang, HY ;

Chen, Y .

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2004, 130 (05) :285-293

[30]

Van de Sande T, 2002, CANCER RES, V62, P642

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