Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Induction of Apoptosis by Vitamin E Succinate in Human Erythroleukemia K562 Cells

인간 만성백혈병 세포주에서의 Vitamin E Succinate에 의한 세포사멸 유도

  • Published : 2007.07.30
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Abstract

Regulation mechanism of apoptosis has been known to be important for understanding the pathogenesis of a number of human diseases including cancers. The effects of $RRR-{\alpha}-tocopheryl$ succinate(vitamin E succinate, VES) on the cell viability, generation of ROS, expression of proteins involved in apoptosis, and growth of human chronic myelogenous leukemia K562 cells were analyzed in this study. VES treatment not only induced the generation of the ROS but also increased the levels of $NF-{\kappa}B$, COX-2, and $p21^{WAF1/CIP1}$ in K562 cells. It modulates the levels of pro-apoptotic proteins such as Bax provoking the apoptosis in K562 cells. The cleavage of PARP into 89 kDa was also increased upon VES treatment in a dosage-dependent manner. Induction of an apoptosis was evident by the increase of sub-Gl peak and cell shrinkage condensed chromatin in K562 cells treated with VES. It also resulted in an inhibition of tumor growth by 50% and prolonged survival of the Iymphoma-induced mice. This potentiation of VES obtained in vitro and in vivo may indicate the feasibility of more effective chemotherapy in chronic myelogenous leukemia.

비타민 E 유도체인 $RRR-{\alpha}-tocopheryl$ succinate (vitamin E succinate, VES)는 만성골수성 백혈병 세포인 K562세포에서 apoptosis를 유도하였다. VES의 처리에 의해 apoptosis가 유도되는 과정에서 K562 세포 내의 ROS의 생성이 증가되었으며, ROS와 관련된$NF-{\kappa}B$, COX-2 그리고 $p21^{WAF1/CIP1}$등의 유전자가 활성화되었다. 뿐만 아니라, apoptosis의 과정 중 중요한 역할을 하는 Bax의 발현증가 및 손상된 DNA의 회복에 중심적 기능을 하는 PARP의 분열이 야기되었다. VES를 처리한 세포의 세포주기 분석에서는 apoptotic phase인 sub-Gl phase에서 세포사멸이 증가되고, 형태적으로는 염색질의 응축이 일어나는 결과로 미루어볼 때 VES는 K562세포의 apoptosis를 유도한 것을 알 수 있다. C57BL/C의 림프종 이종이식을 통한 VES의 항암활성 실험 결과, C57BL/C의 대조군에 비하여 종양의 성장억제를 확인하였으며 높은 생존율을 확인하였다. 이러한 결과는 백혈병 치료에 대한 분자적 기초를 제공하였으며 동물실험을 통하여 보다 실질적인 백혈병 치료의 가능성을 보여주었다.

Keywords

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