Korean J Pediatr.  2009 Jun;52(6):696-700. 10.3345/kjp.2009.52.6.696.

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

Affiliations
  • 1Department of Pediatrics, Wonkwang University School of Medicine, Iksan, Korea. cdy8118@wonkwang.ac.kr
  • 2Department of Family Medicine, Wonkwang University School of Medicine, Iksan, Korea.
  • 3Zoonosis Research Center, Wonkwang University School of Medicine, Iksan, Korea.

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.

Keyword

Compound-127; Endoperoxide ring; Artemisinin; Leukemia apoptosis
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