Tannic acid-induced apoptosis and -enhanced sensitivity to arsenic trioxide in human leukemia HL-60 cells.
Tannic acid (TA), a glucoside of gallic acid polymer, has been shown to possess anti-bacterial, anti-enzymatic, anti-tumor and astringent properties. However, the anti-cancer activity of TA in leukemia is still obscure. In this study, we showed TA-induced apoptotic death in acute myeloid leukemia (AML) HL-60 cells via dose- and time-dependent manner as well as increase of sub-G1 fraction, chromosome condensation, and DNA fragmentation. Further analysis demonstrated the involvement of activation of caspase cascade, cleavage of poly (ADP-ribose) polymerase (PARP), disruption of mitochondrial membrane potential, and release of Cytochrome C, in TA-induced apoptosis. These effects were probably associated with the increase of intracellular superoxide in mitochondrial signaling pathway which attributed to the down-regulation of superoxide dismutase (SOD). Notably, a low dose of TA is sufficient to aggravate arsenic trioxide (As(2)O(3))-induced cytotoxicity in HL-60 cells. Altogether, this study suggested the effects of TA to induce apoptosis in HL-60 and therapeutic potential in AML by being an adjunct to As(2)O(3).
Chen
Kuo-Shuen
KS
Institute of Medicine, Chung Shan Medical University, No. 110 Section 1, Chien Kuo N. Road, Taichung 402, Taiwan.
Hsiao
Yung-Chin
YC
Kuo
Dong-Yih
DY
Chou
Ming-Chih
MC
Chu
Shu-Chen
SC
Hsieh
Yih-Shou
YS
Lin
Tseng-Hsi
TH
D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013634:Tannins / Q000494:pharmacology*
D001152:Arsenicals; D010087:Oxides; D013634:Tannins; D013482:Superoxide Dismutase; D000077237:Arsenic Trioxide