John Franklin, George Jinu, Vartak Supriya V, Srivastava Mrinal, Hassan P A, Aswal V K, Karki Subhas S, Raghavan Sathees C
Biotechnology Laboratory, Department of Chemistry, Sacred Heart College, Kochi, 682 013, India.
Macromol Biosci. 2015 Apr;15(4):521-34. doi: 10.1002/mabi.201400480. Epub 2014 Dec 16.
5,6-Bis(benzylideneamino)-2-mercaptopyrimidin-4-ol (SCR7) is a new anti cancer molecule having capability to selectively inhibit non-homologous end joining (NHEJ), one of the DNA double strand break (DSB) repair pathways inside the cells. In spite of the promising potential as an anticancer agent, hydrophobicity of SCR7 decreases its bioavailability. Herein the entrapment of SCR7 in Pluronic copolymer is reported. The size of the aggregates was determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS) which yields an average diameter of 23 nm. SCR7 encapsulated micelles (ES) were also characterized by small-angle neutron scattering (SANS). Evaluation of its biological properties by using a variety of techniques, including Trypan blue, MTT and Live-dead cell assays, reveal that encapsulated SCR7 can induce cytotoxicity in cancer cell lines, being more effective in breast cancer cell line. Encapsulated SCR7 treatment resulted in accumulation of DNA breaks within the cells, resulting in cell cycle arrest at G1 phase and activation of apoptosis. More importantly, we found ≈ 5 fold increase in cell death, when encapsulated SCR7 was used in comparison with SCR7 alone.
5,6-双(亚苄基氨基)-2-巯基嘧啶-4-醇(SCR7)是一种新型抗癌分子,能够选择性抑制非同源末端连接(NHEJ),这是细胞内DNA双链断裂(DSB)修复途径之一。尽管SCR7作为抗癌剂具有很大潜力,但其疏水性降低了其生物利用度。本文报道了SCR7被包裹在普朗尼克共聚物中的情况。通过透射电子显微镜(TEM)和动态光散射(DLS)测定聚集体的大小,其平均直径为23 nm。SCR7包封的胶束(ES)也通过小角中子散射(SANS)进行了表征。使用包括台盼蓝、MTT和活死细胞检测在内的多种技术对其生物学特性进行评估,结果表明包封的SCR7可在癌细胞系中诱导细胞毒性,对乳腺癌细胞系更有效。包封的SCR7处理导致细胞内DNA断裂积累,导致细胞周期停滞在G1期并激活细胞凋亡。更重要的是,我们发现与单独使用SCR7相比,使用包封的SCR7时细胞死亡增加了约5倍。