Lysophosphatidic acid induces STAT3 phosphorylation and ovarian cancer cell motility: Their inhibition by curcumin

被引：78

作者：

Seo, Ji Hye ^{[1
]}

Jeong, Kang Jin ^{[1
]}

Oh, Woo Jin ^{[1
]}

Sul, Hae Jeong ^{[1
]}

Sohn, Jang Sihn ^{[1
]}

Kim, Yong Kee ^{[2
]}

Cho, Do Yeun ^{[1
]}

Kang, Jae Ku ^{[1
]}

Park, Chang Gyo ^{[1
]}

Lee, Hoi Young ^{[1
]}

机构：

[1] Konyang Univ, Coll Med, Myunggok Med Res Inst, Taejon 302718, South Korea

[2] Kwandong Univ, Coll Med, Dept Pharmacol, Kangnung 210701, South Korea

来源：

CANCER LETTERS | 2010年 / 288卷 / 01期

关键词：

Curcumin; Lysophosphatidic acid; Ovarian cancer; Motility; Signal transducers; Activators of transcription 3; KAPPA-B; CARCINOMA-CELLS; ACTIVATION; EXPRESSION; PROLIFERATION; MIGRATION; INVASION; GROWTH;

D O I：

10.1016/j.canlet.2009.06.023

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Lysophosphatidic acid (LPA) is a biolipid that stimulates tumor cell invasion and metastasis. In this report, we determined the role of signal transducers and activators of transcription 3 (STAT3) and the effect of a chemopreventive agent, curcumin, on LPA-induced ovarian cancer cell motility. LPA phosphorylated STAT3 in a dose-dependent manner. Treatment of cells with a JAK/STAT inhibitor, AG490. inhibited LPA-induced cell motility. In contrast, transfection of a constitutively active form of STAT3 induced ovarian cancer cell motility. LPA also stimulated interleukin (IL)-6 and IL-8 secretion, which results in STAT3 phosphorylation. Treatment of the cells with curcumin inhibited LPA-induced IL-6 and IL-8 secretion and STAT3 phosphorylation, leading to blocked ovarian cancer cell motility. Collectively, the present study shows the critical role of STAT3 in ovarian cancer cell motility and that this process can be prevented by curcumin. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

引用

页码：50 / 56

页数：7

共 29 条

[1] Molecular targets of dietary agents for prevention and therapy of cancer [J].

Aggarwal, BB ;

Shishodia, S .

BIOCHEMICAL PHARMACOLOGY, 2006, 71 (10) :1397-1421

[2] Inhibition of growth and survival of human head and neck squamous cell carcinoma cells by curcumin via modulation of nuclear factor-κB signaling [J].

Aggarwal, S ;

Takada, Y ;

Singh, S ;

Myers, JN ;

Aggarwal, BB .

INTERNATIONAL JOURNAL OF CANCER, 2004, 111 (05) :679-692

[3] Curcumin (diferuloylmethane) down-regulates expression of cell proliferation and antiapoptotic and metastatic gene products through suppression of IκBα kinase and Akt activation [J].

Aggarwal, S ;

Ichikawa, H ;

Takada, Y ;

Sandur, SK ;

Shishodia, S ;

Aggarwal, BB .

MOLECULAR PHARMACOLOGY, 2006, 69 (01) :195-206

[4] Curcurnin (diferuloylmethane) inhibits constitutive and IL-6-inducible STAT3 phosphorylation in human multiple myeloma cells [J].

Bharti, AC ;

Donato, N ;

Aggarwal, BB .

JOURNAL OF IMMUNOLOGY, 2003, 171 (07) :3863-3871

[5] Stat3 as an oncogene [J].

Bromberg, JF ;

Wrzeszczynska, MH ;

Devgan, G ;

Zhao, YX ;

Pestell, RG ;

Albanese, C ;

Darnell, JE .

CELL, 1999, 98 (03) :295-303

[6] Inhibition of growth and sensitization to cisplatin-mediated killing of ovarian cancer cells by polyphenolic chemopreventive agents [J].

Chan, MM ;

Fong, D ;

Soprano, KJ ;

Holmes, WF ;

Heverling, H .

JOURNAL OF CELLULAR PHYSIOLOGY, 2003, 194 (01) :63-70

[7] THE BIOACTIVE PHOSPHOLIPID LYSOPHOSPHATIDIC ACID IS RELEASED FROM ACTIVATED PLATELETS [J].

EICHHOLTZ, T ;

JALINK, K ;

FAHRENFORT, I ;

MOOLENAAR, WH .

BIOCHEMICAL JOURNAL, 1993, 291 :677-680

[8] Mechanisms for lysophosphatidic acid-induced cytokine production in ovarian cancer cells [J].

Fang, XJ ;

Yu, SX ;

Bast, RC ;

Liu, SY ;

Xu, HJ ;

Hu, SX ;

LaPushin, R ;

Claret, FX ;

Aggarwal, BB ;

Lu, YL ;

Mills, GB .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (10) :9653-9661

[9] Lysophosphatidic acid is a bioactive mediator in ovarian cancer [J].

Fang, XJ ;

Schummer, M ;

Mao, ML ;

Yu, SX ;

Tabassam, FH ;

Swaby, R ;

Hasegawa, Y ;

Tanyi, JL ;

LaPushin, R ;

Eder, A ;

Jaffe, R ;

Erickson, J ;

Mills, GB .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2002, 1582 (1-3) :257-264

[10] EXPRESSION OF CELL-ADHESION MOLECULES ON OVARIAN TUMOR-CELL LINES AND MESOTHELIAL CELLS, IN RELATION TO OVARIAN-CANCER METASTASIS [J].

GARDNER, MJ ;

JONES, LMH ;

CATTERALL, JB ;

TURNER, GA .

CANCER LETTERS, 1995, 91 (02) :229-234

← 1 2 3 →