Nawale Laxman, Dubey Parul, Chaudhari Bhushan, Sarkar Dhiman, Prabhune Asmita
Combichem-Bioresource Center, OCD, National Chemical Laboratory, Pune, India.
Biochemical Sciences Division, National Chemical Laboratory, Pune, India.
PLoS One. 2017 Apr 18;12(4):e0174241. doi: 10.1371/journal.pone.0174241. eCollection 2017.
Sophorolipids (SLs) are glycolipid biosurfactants that have been shown to display anticancer activity. In the present study, we report anti-proliferative studies on purified forms of novel SLs synthesized using cetyl alcohol as the substrate (referred as SLCA) and their anticancer mechanism in human cervical cancer cells. Antiproliferative effect of column purified SLCA fractions (A, B, C, D, E and F) was examined in panel of human cancer cell lines as well as primary cells. Among these fractions, SLCA B and C significantly inhibited the survival of HeLa and HCT 116 cells without affecting the viability of normal human umbilical vein endothelial cells (HUVEC). The two fractions were identified as cetyl alcohol sophorolipids with non-hydroxylated tail differing in the degree of acetylation on sophorose head group. At an IC50 concentration SLCA B (16.32 μg ml-1) and SLCA C (14.14 μg ml-1) blocked the cell cycle progression of HeLa cells at G1/S phase in time-dependent manner. Moreover, SLCA B and SLCA C induced apoptosis in HeLa cells through an increase in intracellular Ca2+ leading to depolarization of mitochondrial membrane potential and increase in the caspase-3, -8 and -9 activity. All these findings suggest that these SLCAs could be explored for their chemopreventive potential in cervical cancer.
槐糖脂(SLs)是一类糖脂生物表面活性剂,已被证明具有抗癌活性。在本研究中,我们报告了以十六醇为底物合成的新型SLs纯化形式(称为SLCA)的抗增殖研究及其在人宫颈癌细胞中的抗癌机制。在一组人癌细胞系以及原代细胞中检测了柱纯化的SLCA组分(A、B、C、D、E和F)的抗增殖作用。在这些组分中,SLCA B和C显著抑制了HeLa和HCT 116细胞的存活,而不影响正常人脐静脉内皮细胞(HUVEC)的活力。这两个组分被鉴定为十六醇槐糖脂,其非羟基化尾部在槐糖头部基团上的乙酰化程度不同。在IC50浓度下,SLCA B(16.32μg/ml)和SLCA C(14.14μg/ml)以时间依赖性方式阻断HeLa细胞在G1/S期的细胞周期进程。此外,SLCA B和SLCA C通过增加细胞内Ca2+诱导HeLa细胞凋亡,导致线粒体膜电位去极化,并增加caspase-3、-8和-9的活性。所有这些发现表明,这些SLCA可用于探索其在宫颈癌中的化学预防潜力。