Ascorbic acid synergistically potentiates phloxine b-induced photocytotoxicity in human acute promyelocytic leukemia cells.

Abstract

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.

• Authors: Hang Qi, Qian Wu, Naomi Abe, Shunya Saiki, Beiwei Zhu, Yoshiyuki Murata, Yoshimasa Nakamura
• Journal: Journal of biochemical and molecular toxicology (J Biochem Mol Toxicol) Vol. 28 Issue 4 Pg. 167-73 (Apr 2014) ISSN: 1099-0461 [Electronic] United States
• PMID: 24488945 (Publication Type: Journal Article)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• Antineoplastic Agents
• Photosensitizing Agents
• JNK Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• CASP3 protein, human
• Caspase 3
• Glutathione
• Eosine I Bluish
• Ascorbic Acid

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis
• Ascorbic Acid (pharmacology)
• Caspase 3 (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• DNA Fragmentation
• Drug Synergism
• Eosine I Bluish (pharmacology)
• Glutathione (metabolism)
• HL-60 Cells
• Humans
• JNK Mitogen-Activated Protein Kinases (metabolism)
• MAP Kinase Signaling System
• Oxidative Stress
• Phosphorylation
• Photosensitizing Agents (pharmacology)
• Protein Processing, Post-Translational
• p38 Mitogen-Activated Protein Kinases (metabolism)