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Ciglitizone Inhibits Cell Proliferation in Human Uterine Leiomyoma via Activation of Store-Operated Ca2+ Channels

Ciglitizone Inhibits Cell Proliferation in Human Uterine Leiomyoma via Activation of Store-Operated Ca2+ Channels

Byoung Ywong Kim, Chi-Heum Cho, Dae-Kyu Song, Kyo-Cheol Mun, Seong-Il Suh, Sang-Pyo Kim, Dong-Hoon Shin, Byeong-Churl Jang, Taeg Kyu Kwon, Soon-Do Cha, Insoo Bae, Jae Hoon Bae

Am J Physiol Cell Physiol. 2005 Feb;288(2):C389-95.

PMID: 15469956

Abstract:

This study investigated the acute effects of a peroxisome proliferator-activated receptor (PPAR)-gamma ligand, ciglitizone, on cell proliferation and intracellular Ca2+ signaling in human normal myometrium and uterine leiomyoma. Changes in intracellular Ca2+ concentration ([Ca2+]i) were measured with fura-2 AM, and cellular viabilities were determined by viable cell count and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide reduction assay. Ciglitizone (100 microM) induced greater inhibition of cell proliferation in uterine leiomyoma than in myometrium. Ciglitizone also dose-dependently increased [Ca2+]i in both myometrium and uterine leiomyoma; these [Ca2+]i increases were inhibited by PPAR-gamma antagonists and raloxifene. Ciglitizone-induced [Ca2+]i increase showed only an initial peak in normal myometrial cells, whereas in uterine leiomyoma there was a second sustained [Ca2+]i increase as well. The initial [Ca2+]i increase in both myometrium and uterine leiomyoma resulted from the release of Ca2+ by the sarcoplasmic reticulum via activation of ryanodine receptors. The second [Ca2+]i increase was observed only in uterine leiomyoma because of a Ca2+ influx via an activation of store-operated Ca2+ channels (SOCCs). Cell proliferation was inhibited and secondary [Ca2+]i increase in uterine leiomyoma was attenuated by cotreatment of ciglitizone with a SOCC blocker, lanthanum. The results suggest that ciglitizone inhibits cell proliferation and increases [Ca2+]i through the activation of SOCCs, especially in human uterine leiomyoma.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP74772773-B	Ciglitizone		74772-77-3	Price

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