Ascorbic acid synergistically potentiates phloxine b-induced photocytotoxicity in human acute promyelocytic leukemia cells.
Ascorbic acid (AsA) is known as an antioxidant but concomitantly possesses a pro-oxidant property. Because the impact of AsA on photodynamic therapy response is unclear, we investigated the effect of AsA on photocytotoxicity induced by phloxine B in human acute promyelocytic leukemia HL-60 cells. AsA synergistically enhanced phloxine B-induced photocytotoxic effects, including inhibition of cell proliferation, DNA ladder formation, and caspase-3 activation, whereas AsA itself showed no photocytotoxicity. AsA also enhanced the consumption of the reduced glutathione level compared with the cells treated with phloxine B alone under the light condition. Combination of AsA with phloxine B under the light condition enhanced the phosphorylation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase (MAPK). These effects were completely cancelled by catalase. These results suggest that AsA synergistically enhances phloxine B-induced photocytotoxicity, possibly through the extracellular oxidative stress-dependent MAPK pathway activation.
School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, People's Republic of China.
Hang
H
Qi
Qian
Q
Wu
Naomi
N
Abe
Shunya
S
Saiki
Beiwei
B
Zhu
Yoshiyuki
Y
Murata
Yoshimasa
Y
Nakamura
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001205:Ascorbic Acid / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation; D004357:Drug Synergism; D010697:Eosine I Bluish / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D018384:Oxidative Stress; D010766:Phosphorylation; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D005978:Glutathione; D010697:Eosine I Bluish; D001205:Ascorbic Acid
Ascorbic Acid; HL-60 Cells; Hydrogen Peroxide; Phloxine B; Photocytotoxicity