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

Ji Hye Seo; Kang Jin Jeong; Woo Jin Oh; Hae Jeong Sul; Jang Sihn Sohn; Yong Kee Kim; Do Yeun Cho; Jae Ku Kang; Chang Gyo Park; Hoi Young Lee

doi:10.1016/j.canlet.2009.06.023

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

Cancer Lett. 2010 Feb 1;288(1):50-6. doi: 10.1016/j.canlet.2009.06.023. Epub 2009 Jul 31.

Authors

Ji Hye Seo¹, Kang Jin Jeong, Woo Jin Oh, Hae Jeong Sul, Jang Sihn Sohn, Yong Kee Kim, Do Yeun Cho, Jae Ku Kang, Chang Gyo Park, Hoi Young Lee

Affiliation

¹ Myunggok Medical Research Institute, College of Medicine, Konyang Univeristy, Daejeon 302-718, Republic of Korea.

PMID: 19647363
DOI: 10.1016/j.canlet.2009.06.023

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents, Phytogenic / pharmacology*
Cell Line, Tumor
Cell Movement / drug effects*
Cell Survival / drug effects
Curcumin / pharmacology*
Dose-Response Relationship, Drug
Female
Humans
Interleukin-6 / metabolism
Interleukin-8 / metabolism
Janus Kinases / antagonists & inhibitors
Janus Kinases / metabolism
Lysophospholipids / metabolism*
Neoplasm Invasiveness
Ovarian Neoplasms / metabolism
Ovarian Neoplasms / pathology*
Phosphorylation
Protein Kinase Inhibitors / pharmacology
STAT3 Transcription Factor / antagonists & inhibitors
STAT3 Transcription Factor / genetics
STAT3 Transcription Factor / metabolism*
Signal Transduction / drug effects
Transfection
Tyrphostins / pharmacology

Substances

Antineoplastic Agents, Phytogenic
CXCL8 protein, human
IL6 protein, human
Interleukin-6
Interleukin-8
Lysophospholipids
Protein Kinase Inhibitors
STAT3 Transcription Factor
STAT3 protein, human
Tyrphostins
alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
Janus Kinases
Curcumin
lysophosphatidic acid