sphingosine kinase1 involves the inhibitory action of hif1 by chlorogenic acid in hypoxic du145 cells hypoxia enhances cancer development in a solid tumor hypoxiainducible factor1 hif1 is a transcription factor that is dominantly expressed under hypoxia in solid tumor cells and is a key factor that regulates tumor hif1 regulates several target genes involved in many aspects of cancer progression including angiogenesis metastasis antiapoptosis and cell proliferation as well as imparts resistance to cancer treatment in this study we assessed crataegus pinnatifida bunge var typical schneider ethanol extract cpe for its anticancer effects in hypoxiainduced du145 human prostate cancer cell line cpe decreased the abundance of hif1 and sphingosine kinase1 sphk1 in hypoxiainduced prostate cancer du145 cells cpe decreased hif1 and sphk1 as well as sphk1 activity chlorogenic acid ca is one of four major compounds of cpe compared to cpe ca significantly decreased the expression of hif1 and sphk1 as well as sphk1 activity in hypoxiainduced du145 cells furthermore ca decreased phosphorylation akt and gsk3 which are associated with hif1 stabilization and affected sphk1 in a concentrationdependent manner we confirmed the mechanism of cainduced inhibition of hif1 by sphk1 signaling pathway using sphk1 sirna and sphk inhibitor ski ca decreased the secretion and cellular expression of vegf thus inhibiting hypoxiainduced angiogenesis treatment of du145cells with sphk1 sirna and ca for 48 h decreased cancer cell growth and the inhibitory action of sphk sirna and ca on cell growth was confirmed by decrease in the abundance of proliferating cell nuclear antigen pcna