Quercetin Induces Oxidative Stress and Potentiates the Apoptotic Action of 2-Methoxyestradiol in Human Hepatoma Cells

Abstract

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.

Quercetin modulates Nrf2 and glutathione-related defenses in HepG2 cells: Involvement of p38

“…Quercetin is consumed in the diet and a large body of evidence indicates that it has potent chemopreventive effects against a variety of malignant cell lines and in murine carcinoma models [4,7,10].…”

“…The capacity of cells to maintain homeostasis during oxidative stress resides in the induction of protective enzymes, as well as non-enzymatic defenses such as GSH [5,7,8,[18][19][20]22, 44], playing Nrf2 an important role in the regulation of these processes [8,16,21,24].…”

“…Many studies have demonstrated that quercetin exerts potential anticarcinogenic activities, since it is a potent inhibitor of tumor initiation in vivo [4], is a powerful radical scavenger able to prevent or delay conditions which favor cellular oxidative stress [5,6], possesses anti-proliferative activities against tumor cells in vitro [4,7,8], and induces apoptosis in different cancer cell lines by modulating a number of key elements in cellular signal transduction pathways linked to the apoptotic cell death [1,[7][8][9][10][11][12].…”

Quercetin-mediated apoptosis via activation of the mitochondrial-dependent pathway in MG-63 osteosarcoma cells

“…1), is an abundant flavonoid in tea, fruits and vegetables (6). Quercetin has been shown to induce cell death by apoptosis in many human cancer cell lines, such as hepatoma, oral, leukemia, lung and colon cancer cell lines (7,8).…”

“…1), is an abundant flavonoid in tea, fruits and vegetables (6). Quercetin has been shown to induce cell death by apoptosis in many human cancer cell lines, such as hepatoma, oral, leukemia, lung and colon cancer cell lines (7,8).Apoptotic cell death is an innate cellular response to eliminate abnormal or redundant cells in mammals and hence is crucial for mammal development and tissue homeostasis (9). The disturbed regulation of this vital process represents a major causative factor in the pathogenesis of cancers, including OS (10,11).…”