Sensitization of tumor cells toward chemotherapy: Enhancing the efficacy of camptothecin with imidazolines
Sensitization of tumor cells toward chemotherapy: Enhancing the efficacy of camptothecin with imidazolines
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DOI：
10.1016/j.chembiol.2004.10.006
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发表时间：
2004-12-01
影响因子：
--
通讯作者：
Tepe, JJ
中科院分区：
文献类型：
--
作者：
Sharma, V;Lansdell, TA;Tepe, JJ
研究发现，化疗药物激活核转录因子κ b （nf - κ b）可保护细胞免于凋亡。鉴于nf - kappab在调节细胞对凋亡药物耐药性中的核心作用，抑制nf - kappab介导的基因转录可能使肿瘤细胞对化疗药物敏感并增强其疗效。我们在此描述了一种非细胞毒性咪唑啉支架，使白血病T细胞对化疗药物喜树碱敏感。咪唑啉未明显诱导细胞凋亡；然而，用这种药物预处理细胞导致喜树碱的功效急剧增强（类似于75倍）。潜在细胞机制的阐明表明咪唑啉可阻止NF-kappaB的核易位。这些发现表明，这种咪唑啉抑制NF-kappaB可能为癌症的化疗治疗提供改进的策略。
Activation of nuclear transcription factor kappaB (NF-kappaB) by chemotherapeutic agents was found to protect cells from apoptosis. In light of its central role in regulating the cellular resistance to apoptotic agents, inhibition of NF-kappaB-mediated gene transcription may sensitize tumor cells to chemotherapeutic agents and enhance their efficacy. We describe herein a noncytotoxic imidazoline scaffold that sensitizes leukemia T cells to the chemotherapeutic agent camptothecin. No significant induction of apoptosis was found when cells were treated with the imidazoline; however, pretreatment of cells with this agent resulted in a drastic enhancement in efficacy of camptothecin (similar to75-fold). Elucidation of the potential cellular mechanism revealed that the imidazoline prevents nuclear translocation of NF-kappaB. These findings indicate that inhibition of NF-kappaB by this imidazoline may present improved strategies in the chemotherapeutic treatment of cancer.