Mitochondrial targeting drug lonidamine triggered apoptosis in doxorubicin-resistant HepG2 cells
Mitochondrial targeting drug lonidamine triggered apoptosis in doxorubicin-resistant HepG2 cells
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DOI：
10.1016/s0024-3205(02)02103-3
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发表时间：
2002-10-25
期刊：
影响因子：
6.1
通讯作者：
Kong, SK
中科院分区：
文献类型：
--
作者：
Li, YC;Fung, KP;Kong, SK
线粒体在细胞凋亡的诱导和执行中起着至关重要的作用。因此，最近有人建议使用直接作用于线粒体的试剂来触发细胞凋亡，从而可以消除药物敏感性和耐药性肿瘤细胞。为了验证这一假设，我们以人肝癌细胞HepG 2及其衍生物R-HepG 2为研究对象，研究了新型线粒体靶向药物氯尼达明（LND）诱导细胞凋亡的作用。我们的研究结果表明，R-HepG 2细胞对LND比亲本细胞更敏感，在细胞毒性方面通过阿利兰测定。LND诱导的细胞死亡与细胞凋亡的标志有关，如线粒体膜去极化、细胞色素c释放、磷脂酰丝氨酸外化和DNA片段化。此外，用Dox和LND联合处理细胞引起更多的细胞死亡。总之，我们的研究结果表明，LND作为一种抗癌药物的潜在用途，可以绕过耐药性，并通过HepG 2和R-HepG 2细胞的凋亡引发肿瘤破坏。(C)2002年爱思唯尔科技有限公司All rights reserved.
Mitochondria play a crucial role in the induction and execution of apoptosis. Accordingly, recent suggestions have been made to use agents that directly act on mitochondria to trigger apoptosis so that drug-sensitive and-resistant tumour cells can be eliminated. To test this hypothesis, human hepatocarcinoma HepG2 and its derivative R-HepG2 with doxorubicin (Dox) resistance as a result of expression of P-glycoprotein were used to investigate the effect of lonidamine (LND), a new mitochondrial targeting drug, on the induction of apoptosis. Results from our study indicate that R-HepG2 cells were more sensitive to LND than parental cells in terms of cytotoxicity determined by alamar blue assay. Cell death induced by LND was associated with the hallmarks of apoptosis such as mitochondrial membrane depolarization, release of cytochrome c, phosphatidyl-serine externalization and DNA fragmentation. Moreover, combined treatment of cells with Dox and LND elicited more cell death. Taken together, our results suggest a potential use of LND as an anti-cancer drug to bypass drug resistance and to trigger tumour destruction through apoptosis in HepG2 and R-HepG2 cells. (C) 2002 Elsevier Science Inc. All rights reserved.