Triptolide, a Chinese herbal extract, enhances drug sensitivity of resistant myeloid leukemia cell lines through downregulation of HIF-1α and Nrf2.
OBJECTIVE
To explore whether triptolide (TPL) can enhance drug sensitivity of resistant myeloid leukemia cell lines through downregulation of HIF-1α and Nrf2.


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.


CONCLUSIONS
TPL is able to enhance drug sensitivity of resistant myeloid leukemia cell lines through downregulation of HIF-1α and Nrf2.
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
Feili
F
Chen
Yuejian
Y
Liu
Shiyun
S
Wang
Xutao
X
Guo
Pengcheng
P
Shi
Weiguang
W
Wang
Bing
B
Xu
D045744:Cell Line, Tumor; D004224:Diterpenes / Q000737:chemistry; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis*; D010616:Phenanthrenes / Q000737:chemistry
D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D004852:Epoxy Compounds; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010616:Phenanthrenes; C001899:triptolide