Curcumin downregulates H19 gene transcription in tumor cells

Curcumin (diferuloymethane), a natural compound used in traditional medicine, exerts all antiproliferative effect on various tumor cell lines by an incompletely understood mechanism. It has been shown that low doses of curcumin downregulate DNA topoisomerase II alpha (TOP2A) which is upregulated in many malignances. The activity of TOP2A is required for RNA polymerase II transcription on chromatin templates. Recently, it has been reported that CTCF, a multifunctional transcription factor, recruits the largest subunit of RNA polymerase II (LS Pol II) to its target sites genome-wide. This recruitment of LS Pol II is more pronounced in proliferating cells than in fully differentiated cells. As expression of imprinted genes is often altered in tumors, we investigated the potential effect Of curcumin treatment on transcription of the imprinted HI 9 gene, located distally from the CTCF binding site, in human tumor cell lines HCT 116, SW 620, HeLa, Cal 27, Hep-2 and Detroit 562. Transcription of TOP2A and concomitantly HI 9 was supressed in all tumor cell lines tested. Monoallelic IGF2 expression was maintained in curcumin-treated cancer cells, indicating the involvement of mechanism/s other than disturbance of CTCF insulator function at the IGF2/H19 locus. Curcumin did not alter HI 9 gene transcription in primary cell Cultures derived from normal human tissues.