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

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 motili...

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Bibliographic Details
Published in:Cancer letters 2010-02, Vol.288 (1), p.50-56
Main Authors: Seo, Ji Hye, Jeong, Kang Jin, Oh, Woo Jin, Sul, Hae Jeong, Sohn, Jang Sihn, Kim, Yong Kee, Cho, Do Yeun, Kang, Jae Ku, Park, Chang Gyo, Lee, Hoi Young
Format: Article
Language:English
Subjects:
Activators of transcription 3
Antineoplastic Agents, Phytogenic - pharmacology
Cell adhesion & migration
Cell culture
Cell Line, Tumor
Cell Movement - drug effects
Cell Survival - drug effects
Curcumin
Curcumin - pharmacology
Cytokines
Dose-Response Relationship, Drug
Female
Hematology, Oncology and Palliative Medicine
Humans
Interleukin-6 - metabolism
Interleukin-8 - metabolism
Janus Kinases - antagonists & inhibitors
Janus Kinases - metabolism
Lysophosphatidic acid
Lysophospholipids - metabolism
Medical prognosis
Medical research
Membranes
Motility
Neoplasm Invasiveness
Ovarian cancer
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Phosphorylation
Protein Kinase Inhibitors - pharmacology
Signal transducers
Signal Transduction - drug effects
STAT3 Transcription Factor - antagonists & inhibitors
STAT3 Transcription Factor - genetics
STAT3 Transcription Factor - metabolism
Studies
Transfection
Tyrphostins - pharmacology
Vascular endothelial growth factor
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Summary: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.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2009.06.023