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Aberrant activation of Hedgehog (Hh) signaling pathway has been linked to the development of cancers. A naturally occurring Hedgehog inhibitor, 3’,6-dimethoxy-3’’,4’’-(methylenedioxy)-2,5-epoxylignan-4’-ol (DMEO), isolated from Piper nigrum, exhibited selective cytotoxicity against human pancreatic (PANC1) with no toxic effect on normal cells. This compound blocked the translocation of GLI transcription factors into the nucleus in PANC1. RNA interferences of the Smoothened (Smo) function in PANC1 treated with the compound downregulated the mRNA expression of Ptch.
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