Kumar Akhilesh, D'Souza Saritha S, Gaonkar S L, Rai K M L, Salimath Bharathi P
Department of Studies in Biotechnology, University of Mysore, Manasagangotri, Mysore, 570006, Karnataka, India.
Invest New Drugs. 2008 Oct;26(5):425-35. doi: 10.1007/s10637-008-9116-5. Epub 2008 Jan 29.
The multiple pharmacological actions of unique synthetic compounds are a prerequisite for classifying a drug as highly efficacious, because the multiple pharmacological actions offer the possibility of treating various diseases like cancer. 1,3,4-Oxadiazoles are an important class of heterocyclic compounds with broad spectrum of biological activities. In this study we focused on the ability of these derivatives to induce apoptosis in cultured MCF-7 breast cancer cells. Treatment of MCF-7 cells with varying concentrations of the different derivatives resulted in dose and time dependent sequence of events marked by apoptosis, as shown by loss of cell viability, chromatin condensation, internucleosomal DNA fragmentation and sub G(0) phase accumulation. Furthermore, apoptosis in MCF-7 cell was induced by upregulation of proto-oncoprotein Bax and activation of Caspase-3 activated DNase. Although the derivatives induced apoptosis was associated with Bax protein levels, negligible Bcl-2 reduction was observed. Analysis of the data suggests that the substituted oxadiazole derivatives exert antiproliferative action and growth inhibition on MCF-7 cells through apoptosis induction and that it may have anticancer properties valuable for application in drug products.
独特合成化合物的多种药理作用是将一种药物归类为高效药物的先决条件，因为多种药理作用为治疗诸如癌症等各种疾病提供了可能性。1,3,4-恶二唑是一类具有广泛生物活性的重要杂环化合物。在本研究中，我们着重关注了这些衍生物诱导培养的MCF-7乳腺癌细胞凋亡的能力。用不同浓度的不同衍生物处理MCF-7细胞，导致出现以凋亡为特征的剂量和时间依赖性事件序列，表现为细胞活力丧失、染色质浓缩、核小体间DNA片段化以及亚G(0)期积累。此外，MCF-7细胞中的凋亡是由原癌蛋白Bax的上调和半胱天冬酶-3激活的脱氧核糖核酸酶的激活所诱导的。虽然衍生物诱导的凋亡与Bax蛋白水平相关，但未观察到Bcl-2有明显降低。数据分析表明，取代的恶二唑衍生物通过诱导凋亡对MCF-7细胞发挥抗增殖作用和生长抑制作用，并且其可能具有在药物产品中应用的有价值的抗癌特性。
