Triptolide, a Chinese herbal extract, enhances drug sensitivity of resistant myeloid leukemia cell lines through downregulation of HIF-1α and Nrf2

Abstract

Aim: To explore whether triptolide (TPL) can enhance drug sensitivity of resistant myeloid leukemia cell lines through downregulation of HIF-1α and Nrf2. Materials & methods: HL60/A and K562/G cells were subjected to different treatments and thereafter an methyl thiazole tetrazolium bromide assay, flow cytometry, western blot and real-time PCR were used to determine IC50, apoptotic status and expression of Nrf2, HIF-1α and their target genes. Results: Doxorubicin- or imatinib-induced apoptosis was enhanced when anticancer agents were used in combination with TPL. When combined with TPL, both doxorubicin and imatinib downregulate Nrf2 and HIF-1α expression at protein and mRNA levels. Genes downstream of Nrf2, for example, NQO1, GSR and HO-1, as well as target genes of HIF-1α, for example, BNIP3, VEGF and CAIX are also downregulated at the mRNA level. Conclusion: TPL is able to enhance drug sensitivity of resistant myeloid leukemia cell lines through downregulation of HIF-1α and Nrf2. Original submitted 7 January 2013; Revision submitted 20 June 2013