Apicidin upregulates PHD2 prolyl hydroxylase gene expression in cervical cancer cells

It was recently reported that the reduced expression of hypoxia-inducible factor prolyl 4-hydroxylase PHD2 in human cancers correlates with increased angiogenesis. We used HeLa, CaSki, C33A, and SiHa cervical cancer cells to show the effect of apicidin on cellular levels of PHD2 enzyme. Using reverse transcription, real-time quantitative PCR, and western blot analysis, we established that apicidin upregulates PHD2 transcript and protein levels in HeLa, CaSki, and C33A, but not in SiHa cervical cancer cells. Bisulfite sequencing showed that the increase in PHD2 expression was accompanied by demethylation of CpG islands located in the first exon of the PHD2 gene. As decreased PHD2 expression supports tumor progression, our findings may validate the usefulness of apicidin as an anticancer drug. Anti-Cancer Drugs 21:619-624 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.