Quercetin induces oxidative stress and potentiates the apoptotic action of 2-methoxyestradiol in human hepatoma cells.
Hepatocellular carcinoma (HCC) is the leading cause of cancer mortality in Asia. This study evaluated the growth inhibition effect of quercetin and 2-methoxyestradiol in vitro in human HCC cell lines. Combination treatment enhanced the cytotoxic effect in HA22T/VGH and HepG2 cell lines as compared with quercetin or 2-methoxyestradiol alone. The cell population of sub-G0/G1 phase and the level of annexin V binding were increased synergistically after combination treatment with quercetin and 2-methoxyestradiol in both cell lines. Moreover, quercetin combined with 2-methoxyestradiol increased superoxide levels, mitochondrial superoxide dismutase (MnSOD) in mRNA, protein levels, and SOD activity. Finally, we also found the mitochondrial membrane potential was decreased after combination treatment. The changes of reactive oxygen species and mitochondrial disruption were likely to be involved in the mechanism for the synergistic cytotoxicity effects of combination treatment in human hepatoma cells. These results provided a basis for further study of the potential usage of quercetin combination with hormonal agents for the treatment of human hepatoma.
Chang
Yuh-Fang
YF
Taipei Veterans General Hospital, Taipei, Taiwan.
Hsu
Yi-Chiung
YC
Hung
Hui-Fang
HF
Lee
Hui-Ju
HJ
Lui
Wing-Yiu
WY
Chi
Chin-Wen
CW
Wang
Jane-Jen
JJ
D000077584:2-Methoxyestradiol; D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000628:therapy; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress; D011794:Quercetin / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000099156:Superoxide Dismutase 2
D000077584:2-Methoxyestradiol; D017304:Annexin A5; D000970:Antineoplastic Agents; D004958:Estradiol; D011794:Quercetin; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2