Combination with water-soluble antioxidants increases the anticancer activity of quercetin in human leukemia cells.
While accumulation of reactive oxygen species (ROS) is believed to be harmful to organisms, recent studies show that quercetin (QU), a promising antioxidant and anticancer drug, exerts its anticancer role through either diminishing or promoting ROS generation under different conditions. In the present study, it was investigated whether the water-soluble antioxidants ascorbic acid (ASA), N-acetyl-cysteine (NAC) and reduced glutathione (GSH) can enhance both the antioxidant and anticancer activity of quercetin in human myeloid leukemia cells (HL-60 cells). Proliferation, viability and ROS accumulation (indicated by the level of malondialdehyde, MDA) was significantly decreased by QU in HL-60 cells. 50 microM H2O2 markedly attenuated the antioxidant and anticancer activity of QU, proving that diminution of ROS accumulation considerably contributes to the QU-induced decrease of HL-60 cells proliferation and viability. When the effects of water-soluble antioxidants were tested, ASA at 1 mM, NAC at 500 microM, or GSH at 250 microM significantly enhanced QU-mediated proliferation arrest, cell death and ROS diminution. These results indicate that certain amounts of ROS are critical for the proliferation and viability of HL-60 cells, while water-soluble antioxidants enhance the anticancer activity of QU through scavenging ROS. Combing QU with water-soluble antioxidants could be a useful strategy to improve the anticancer activity of QU by increasing its antioxidant activity.
Chen
Jie
J
Department of Hematology, Xijing Hospital, the Fourth Military Medicine University, Xi'an, China.
Kang
Jiuhong
J
Da
Wanming
W
Ou
Yingxian
Y
D000111:Acetylcysteine / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000737:chemistry / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D007202:Indicators and Reagents; D007938:Leukemia / Q000188:drug therapy*; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000737:chemistry; D011794:Quercetin / Q000737:chemistry* / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D012995:Solubility
D000970:Antineoplastic Agents; D000975:Antioxidants; D007202:Indicators and Reagents; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D011794:Quercetin; D006861:Hydrogen Peroxide; D005978:Glutathione; D001205:Ascorbic Acid; D000111:Acetylcysteine