| Anti-tumor effect of new compound, 127, through the induction of apoptosis |
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Ki Hwan Baek1, A Lum Han2, Sae Ron Shin2, Chun Mae Jin3, Young Wook Yoon1, Seung Taek Yu1, Jong Duk Kim1, Du Young Choi1 |
1Department of Pediatrics, Wonkwang University School of Medicine, Iksan, Korea
2Department of Family Medicine, Wonkwang University School of Medicine, Iksan, Korea
3Zoonosis Research Center, Wonkwang University School of Medicine, Iksan, Korea |
| 새로운 화합물 c-127의 세포고사 유도에 의한 항암효과 |
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백기환1, 한아름2, 신새론2, 진춘매3, 윤영욱1, 유승택1, 김종덕1, 최두영1 |
1원광대학교 의과대학 소아과학교실
2원광대학교 의과대학 정의학과교실
3인수공통감염병 연구센터 |
Correspondence:
Du Young Choi, Email: cdy8118@wonkwang.ac.kr
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| 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. |
| Key Words:
Compound-127, Endoperoxide ring, Artemisinin, Leukemia apoptosis |
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