Department of Physiology, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece.
Eur J Pharm Sci. 2011 Feb 14;42(3):253-61. doi: 10.1016/j.ejps.2010.11.015. Epub 2010 Dec 3.
Nowadays, investigation for possible therapeutic applications of various metal-based drugs attracts the scientific interest worldwide. The triorganotin compound bistriphenyltin(IV) (SnMNA), was tested for its anti-proliferative and antitumor activities. Cytotoxic activity was assessed by Trypan blue and 3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide assay (MTT). SnMNA exhibited potent cytotoxic effects against leiomyosarcoma cells (LMS) and human breast adenocarcinoma cells (MCF-7), which is 200 times stronger than that of cisplatin. Moreover, SnMNA induced significant apoptosis in LMS and MCF-7 cells characterized by flow cytometry analysis and DNA fragmentation. Acute and chronic toxicity studies on Wistar rats caused kidney and lung toxicity at a single dose of 80mg/kgBody Weight (BW) or four repeated doses of 8mg/kgBW once per week. Furthermore, antitumor activity studies on sarcoma bearing Wistar rats revealed that SnMNA complex at four repeated doses of 5.4mg/kgBW every three days prolonged mean survival time of the animal at 200% and decreased mean tumor growth rate (MTGR) compared to the control group (p<0.05). It is noteworthy to mention that the 30% (3 out of 10) of the bearing animals were totally cured. These findings indicate that SnMNA might be a promising new antitumor agent.
如今,全世界的科学家都在研究各种金属基药物的潜在治疗应用。三丁基锡化合物双[三苯基锡(IV)](3-羧基吡啶-2-硫代)(SnMNA)已被测试其抗增殖和抗肿瘤活性。通过台盼蓝和 3-(4.5-二甲基噻唑-2-基)-2.5-二苯基四氮唑溴盐(MTT)测定法评估细胞毒性活性。SnMNA 对平滑肌肉瘤细胞(LMS)和人乳腺癌细胞(MCF-7)具有很强的细胞毒性作用,其活性比顺铂强 200 倍。此外,SnMNA 诱导 LMS 和 MCF-7 细胞显著凋亡,其特征是通过流式细胞术分析和 DNA 片段化。在 Wistar 大鼠中进行的急性和慢性毒性研究表明,在 80mg/kg 体重(BW)的单次剂量或每周一次重复 8mg/kgBW 的 4 次剂量下,可引起肾脏和肺部毒性。此外,在荷肉瘤的 Wistar 大鼠中进行的抗肿瘤活性研究表明,SnMNA 复合物以 5.4mg/kgBW 的 4 次重复剂量每三天给药一次,与对照组相比,可将动物的平均存活时间延长 200%,并降低平均肿瘤生长率(MTGR)(p<0.05)。值得注意的是,30%(10 只中有 3 只)的荷瘤动物完全治愈。这些发现表明,SnMNA 可能是一种很有前途的新型抗肿瘤药物。