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http://dx.doi.org/10.3345/kjp.2009.52.6.696

Anti-tumor effect of new compound, 127, through the induction of apoptosis  

Baek, Ki Hwan (Department of Pediatrics, Wonkwang University School of Medicine)
Han, A Lum (Department of Family Medicine, Wonkwang University School of Medicine)
Shin, Sae Ron (Department of Family Medicine, Wonkwang University School of Medicine)
Jin, Chun Mae (Zoonosis Research Center, Wonkwang University School of Medicine)
Yoon, Young Wook (Department of Pediatrics, Wonkwang University School of Medicine)
Yu, Seung Taek (Department of Pediatrics, Wonkwang University School of Medicine)
Kim, Jong Duk (Department of Pediatrics, Wonkwang University School of Medicine)
Choi, Du Young (Department of Pediatrics, Wonkwang University School of Medicine)
Publication Information
Clinical and Experimental Pediatrics / v.52, no.6, 2009 , pp. 696-700 More about this Journal
Abstract
Purpose : We screened more than 350 compounds with an endoperoxide ring structure in search of an anti-leukemic drug and found that compound 127 (c-127) could induce significant cytotoxicity in HL-60 cells. In this study, we investigated the molecular mechanisms of compound 127-induced antitumor activity on HL-60 cells. Methods : HL-60 cells were cultured in Rosewell Park Memorial Institute 1640 and cell viability was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], a tetrazole assay. Apoptosis was assessed by a DNA fragmentation test. Apoptotic machineries were determined by Western blot analysis. Results : C-127 could induce a cytotoxic effect at 24 h and apoptosis at 6 h, which was demonstrated with MTT assay and DNA fragmentation test, respectively. The apoptotic effect of this drug was caused by the activation of the intracellular caspase-8,3 activation, the cleavage of pro-apoptotic Bid, and the increase of c-Jun expression accompanied with JNK (Jun N-terminal kinases) phosphorylation. On the contrary, it increased the expression of anti-apoptotic Bcl-2 levels, leading to the induction of the induction of anti-apoptotic effect. Taken together, the present study demonstrated that c-127 was a potent inducer of cytotoxicity on HL-60 cells through apoptotic mechanisms, which included the activation of caspase family, the regulation of Bcl-2 family, and the activation of JNK signaling pathway. Conclusion : Our results suggest that c-127 has a strong antitumor activity through the regulation of various apoptotic machineries on HL-60 cells. The compound may be utilized as an effective and potentially therapeutic drug in leukemia.
Keywords
Compound-127; Endoperoxide ring; Artemisinin; Leukemia apoptosis;
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