Department of Drug Discovery, Science Farm Ltd., 1-7-30-805 Kuhonji, Chuo-ku, Kumamoto, 862-0976, Japan.
Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-Ku, Kumamoto, 8620973, Japan.
Invest New Drugs. 2020 Oct;38(5):1326-1333. doi: 10.1007/s10637-020-00911-8. Epub 2020 Feb 15.
Marine natural products have drawn a great deal of attention as a vital source of new drugs for the last five decades. However, marine organisms in the seas surrounding Turkey (the Black Sea, the Aegean Sea and the Mediterranean Sea) haven't been yet extensively explored. In the present study, three marine organisms (Dysidea avara, Microcosmus sabatieri and Echinaster sepositus) were sampled from the Dardanelles (Turkish Straits System, Western Turkey) by scientific divers, transferred to the laboratory and then were extracted with 70% ethanol. The extracts were tested for their cytotoxic effect against K562, KMS-12PE, A549, and A375 cancer cell lines. The sponge extract elicited the most promising cytotoxic activity, thus it was further evaluated against H929, MCF-7, HeLa, and HCT116 cancer cells. Most of the designated cells showed a considerable sensitivity for the sponge extract particularly H929, K562, KMS-12PE and HeLa cells with IC less than 10 μg/mL. On the contrary, the other two extracts exhibited no cytotoxic activity on all cells at 100 μg/mL concentration. The sponge extract was tested for its capacity to induce apoptosis in cancer cells and to inhibit a panel of tyrosine kinases showing remarkable results. The outcome of this study represents a platform for discovery of new chemotherapeutic agents of marine natural origin.
在过去的五十年中,海洋天然产物作为新药的重要来源引起了极大的关注。然而,土耳其周边海域(黑海、爱琴海和地中海)的海洋生物尚未得到广泛探索。在本研究中,研究人员通过科学潜水员从达达尼尔海峡(土耳其海峡系统,土耳其西部)采集了三种海洋生物(Dysidea avara、Microcosmus sabatieri 和 Echinaster sepositus),将它们转移到实验室,然后用 70%乙醇提取。测试了提取物对 K562、KMS-12PE、A549 和 A375 癌细胞系的细胞毒性作用。海绵提取物表现出最有希望的细胞毒性活性,因此进一步评估了其对 H929、MCF-7、HeLa 和 HCT116 癌细胞的作用。大多数指定的细胞对海绵提取物表现出相当大的敏感性,尤其是 H929、K562、KMS-12PE 和 HeLa 细胞,IC 值低于 10μg/mL。相反,在 100μg/mL 浓度下,其他两种提取物对所有细胞均无细胞毒性活性。测试了海绵提取物在癌细胞中诱导细胞凋亡和抑制一组酪氨酸激酶的能力,结果显著。本研究的结果为发现海洋天然来源的新化疗药物提供了一个平台。