title: Combination with water-soluble antioxidants increases the anticancer activity of quercetin in human leukemia cells.
abstract: 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.
authors.affiliation: Department of Hematology, Xijing Hospital, the Fourth Military Medicine University, Xi'an, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Jiuhong
authors.initials: J
authors.lastname: Kang
authors.forename: Wanming
authors.initials: W
authors.lastname: Da
authors.forename: Yingxian
authors.initials: Y
authors.lastname: Ou
mesh_terms: 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
chemical_list: 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