Singh Meenakshi, Modi Arusha, Narayan Gopeshwar, Singh Sushil K
aDepartment of Pharmaceutics, Indian Institute of Technology (BHU) bCancer Genetics Laboratory, Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
Anticancer Drugs. 2016 Jul;27(6):519-32. doi: 10.1097/CAD.0000000000000357.
Cervical cancer is a major cause of morbidity and mortality in women worldwide. In recent years, benzothiazole analogues have attracted considerable attention in anticancer research. Therefore, in this study, the earlier reported amide series of benzothiazole derivatives were investigated for their antiproliferative activity. The activity of amide derivatives was evaluated using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometric analysis, apoptosis assay, and DNA fragmentation on two human cervical cancer cell lines: SiHa and C33-A. The data reported from this investigation indicated that benzothiazole derivatives show pronounced cytotoxicity in the HPV16-positive SiHa cells compared with HPV-negative C-33A cells. The in-vitro cytotoxicity of the compounds on the HEK-293 noncancer cell line was evaluated to establish selectivity. Cells treated with benzothiazole derivatives showed prominent morphological features as evidenced by cell shrinkage, membrane blebbing, apoptotic nuclei, and DNA fragmentation. The benzothiazole derivatives show accumulation of cells in the sub-G1 and S-phase of the cell cycle in SiHa and C33-A, respectively. In addition, these derivatives exert their beneficial effect by inducing apoptosis, in the chemoprevention of cervical cancer cells, and were further ascertained using a DNA fragmentation assay. The compounds studied showed potent cytotoxic and apoptotic properties against SiHa and C33-A cancer cell lines and thus represent an excellent starting point for further optimization of therapeutically effective anticancer drugs.
宫颈癌是全球女性发病和死亡的主要原因。近年来，苯并噻唑类似物在抗癌研究中备受关注。因此，在本研究中，对早期报道的苯并噻唑衍生物酰胺系列进行了抗增殖活性研究。使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法、流式细胞术分析、凋亡检测和DNA片段化分析，在两种人宫颈癌细胞系SiHa和C33-A上评估了酰胺衍生物的活性。本次研究报告的数据表明，与HPV阴性的C-33A细胞相比，苯并噻唑衍生物在HPV16阳性的SiHa细胞中显示出明显的细胞毒性。评估了这些化合物对HEK-293非癌细胞系的体外细胞毒性以确定其选择性。用苯并噻唑衍生物处理的细胞表现出明显的形态学特征，如细胞收缩、膜泡形成、凋亡核和DNA片段化。苯并噻唑衍生物分别使SiHa和C33-A细胞周期的亚G1期和S期细胞积累。此外，这些衍生物通过诱导凋亡在宫颈癌细胞的化学预防中发挥有益作用，并通过DNA片段化检测进一步得到证实。所研究的化合物对SiHa和C33-A癌细胞系显示出强大的细胞毒性和凋亡特性，因此代表了进一步优化治疗有效的抗癌药物的良好起点。
