Agrawal Sweta, Chaugule Sachin, More Shashank, Rane Gargi, Indap Madhavi
Central Research Laboratory, D. G. Ruparel College, Senapati Bapat Marg, Mahim, Mumbai, 400 016, India.
Biol Res. 2017 Dec 12;50(1):41. doi: 10.1186/s40659-017-0147-2.
The marine environment is a rich source of bioactive natural products. Many of the marine bioactive compounds have been derived successfully from molluscs. Euchelus asper is a marine mollusc which is commonly found in the intertidal rocky regions of the Mumbai coast. The present study was focused on evaluating the anti-angiogenic and anti- proliferative activities of methanolic extract of Euchelus asper (EAME).
The anti-angiogenic activity of EAME (50-800 μg/mL) was assessed by chick chorio-allantoic membrane (CAM) model wherein multiple parameters in the CAM blood vessels were analysed through morphometric and histological investigations. In vitro testing of EAME (5-20 μg/mL) included its cytotoxicity against three different cancer cell lines, its effect on cell proliferation by wound healing assay as well as their relevant molecular mechanisms. Statistical analysis was carried out by two-tailed student's t test for two unpaired groups.
Analysis of CAM revealed that the extract is effective in reducing the branching points of the 1st order blood vessels or capillaries of CAM. Histological analysis of CAM showed significant decrease in capillary plexus and compartmentalization along with increase in mesodermal blood vessels, thus establishing its anti-angiogenicity. Further, EAME exhibited moderate but significant cytotoxicity against A549 non-small cell lung carcinoma cell line. We also demonstrated that the cytotoxicity of EAME in A549 was associated with its apoptotic activity by subG1 phase arrest. Lastly, EAME significantly reduced A549 proliferation by reducing the expression of Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9).
Overall, our study suggested that EAME has potential to inhibit tumour angiogenic and proliferative activity and may be a potential source for development of new anti-cancer pharmaceuticals.
海洋环境是生物活性天然产物的丰富来源。许多海洋生物活性化合物已成功地从软体动物中提取出来。粗糙真蹄螺是一种海洋软体动物,常见于孟买海岸的潮间带岩石区域。本研究的重点是评估粗糙真蹄螺甲醇提取物(EAME)的抗血管生成和抗增殖活性。
采用鸡胚绒毛尿囊膜(CAM)模型评估EAME(50 - 800μg/mL)的抗血管生成活性,通过形态计量学和组织学研究分析CAM血管中的多个参数。EAME(5 - 20μg/mL)的体外测试包括其对三种不同癌细胞系的细胞毒性、通过伤口愈合试验对细胞增殖的影响及其相关分子机制。对两个未配对组进行双尾学生t检验进行统计分析。
对CAM的分析表明,该提取物可有效减少CAM一级血管或毛细血管的分支点。CAM的组织学分析显示毛细血管丛和分隔显著减少,同时中胚层血管增加,从而证实了其抗血管生成作用。此外,EAME对A549非小细胞肺癌细胞系表现出中度但显著的细胞毒性。我们还证明,EAME在A549中的细胞毒性与其通过亚G1期阻滞的凋亡活性有关。最后,EAME通过降低基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)的表达显著降低了A549的增殖。
总体而言,我们的研究表明EAME具有抑制肿瘤血管生成和增殖活性的潜力,可能是开发新型抗癌药物的潜在来源。