Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy.
Research Center for Vaccine and Drug, Research Organization for Health, National Research and Innovation Agency (BRIN), JI. Raya Bogor Km. 46, Cibinong 16911, Indonesia.
Mar Drugs. 2023 Jun 24;21(7):371. doi: 10.3390/md21070371.
Marine compounds represent a varied source of new drugs with potential anticancer effects. Among these, sponges, including those belonging to the Irciniidae family, have been demonstrated to exert cytotoxic effects on different human cancer cells. Here, we investigated, for the first time, the therapeutic effect of an extract (referred as iSP) from the sponge, (Porifera, Dictyoceratida, and Irciniidae) on A375 human melanoma cells. We found that iSP impaired A375 melanoma cells proliferation, induced cell death through caspase-dependent apoptosis and arrested cells in the G1 phase of the cell cycle, as demonstrated via both flow cytometry and qPCR analysis. The proapoptotic effect of iSP is associated with increased ROS production and mitochondrial modulation, as observed by using DCF-DHA and mitochondrial probes. In addition, we performed wound healing, invasion and clonogenic assays and found that iSP was able to restrain A375 migration, invasion and clonogenicity. Importantly, we observed that an iSP treatment modulated the expression of the EMT-associated epithelial markers, E-CAD and N-CAD, unveiling the mechanism underlying the effect of iSP in modulating A375 migration and invasion. Collectively, this study provides the first evidence to support the role of sponge extracts as a potential therapeutic resource for the treatment of human melanoma.
海洋化合物是具有潜在抗癌作用的新药的多样化来源。其中,海绵,包括属于 Irciniidae 科的海绵,已被证明对不同的人类癌细胞具有细胞毒性作用。在这里,我们首次研究了海绵(多孔动物门、Dictyoceratida 和 Irciniidae)提取物(称为 iSP)对 A375 人黑色素瘤细胞的治疗作用。我们发现 iSP 可抑制 A375 黑色素瘤细胞的增殖,通过 caspase 依赖性细胞凋亡诱导细胞死亡,并通过流式细胞术和 qPCR 分析将细胞阻滞在细胞周期的 G1 期。iSP 的促凋亡作用与 ROS 产生和线粒体调节的增加有关,如使用 DCF-DHA 和线粒体探针观察到的那样。此外,我们进行了划痕愈合、侵袭和集落形成实验,发现 iSP 能够抑制 A375 的迁移、侵袭和集落形成能力。重要的是,我们观察到 iSP 处理可调节 EMT 相关上皮标志物 E-CAD 和 N-CAD 的表达,揭示了 iSP 调节 A375 迁移和侵袭的作用机制。总的来说,这项研究首次提供了证据支持海绵提取物作为治疗人类黑色素瘤的潜在治疗资源的作用。