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Curcumin and cyclopamine affect viability and proliferation of ovarian teratomas and ovarian carcinomas

The Hh-Gli signaling pathway plays a crucial role in embryonic development of many organisms, from Drosophila melanogaster to humans. It is essential for the development of various tissues, including the ovaries. In the adult ovary the signaling pathway is active in the granulosa cells, surrounding the follicular cells, which respond to activation with Shh protein and to inhibition with cyclopamine. Aberrant activation of this pathway has been associated with various cancers, which include benign ovarian teratomas and ovarian cancer. Cyclopamine was shown to inhibit Hh-Gli signaling in ovarian cancer, which leads to cell cycle arrest. On the other hand, curcumin has not yet been connected to the Hh-Gli signaling pathway. Curcumin, a polyphenol derived from turmeric, was shown to inhibit tumor growth and angiogenesis in ovarian carcinoma. This compound also positively regulates GSK3activity. Since GSK3affects Gli1 activity, we wanted to investigate the effect of curcumin on the members of the Hh-Gli signaling pathway in benign ovarian teratoma and ovarian cancers. In order to investigate the effects of cyclopamine and curcumin, we developed primary cell cultures from human ovarian teratoma and ovarian carcinoma. We established that both compounds have inhibitory effects on cell proliferation and they both affect the expression of the Hh-Gli pathway genes. On the other hand adding exogenous Shh protein to these cell cultures induced them to proliferate, suggesting that these cells are fully capable of transmitting the Hedgehog signal.

curcumin; cyclopamine; Hh-Gli signaling pathway

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