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Molecular perspective on starfish tissue extracts: targeting human carcinoma KB cells for anticancer therapy
Journal of King Saud University-Science ( IF 3.8 ) Pub Date : 2023-11-27 , DOI: 10.1016/j.jksus.2023.103035
Prithiviraj Nagarajan , Sivakumar Allur Subramanian , Chandramohan Govindasamy , Ahmed S. El Newehy , Leena Rajathy Port Louis , Mohan Sivanandham , Kumar Rangarajalu , Casimeer C. Sangeetha , Ahmad Y Ghidan , Alaa Yousef Ghidan

The marine environment is rich in natural bioactive compounds, including zebrafish and starfish species, which have garnered attention in drug research for their remarkable tissue regeneration abilities. Zebrafish, in particular, share a genetic resemblance of around 70% with humans. We chose to investigate Luidia maculata, a starfish species, due to its remarkable tissue regeneration abilities and the potential bioactive compounds it holds, making it a promising candidate for anticancer and antioxidant therapies. Human KB carcinoma cells were subjected to L. maculata tissue extracts to assess cytotoxicity using the MTT test. Intracellular ROS levels were measured via DCFH-DA, and mitochondrial membrane potential changes were evaluated using Rh-123 staining. Oxidative DNA damage was examined with the comet test, while morphological apoptotic changes were observed through the AO/EtBr dual staining technique. The active compounds in the starfish extracts were identified using HPLC, GC-MS/MS, and FTIR analyses. The bioactive fractions extracted from L. maculata demonstrated significant anti-proliferative effects on KB carcinoma cells, inducing apoptosis. These fractions led to a notable increase in intracellular ROS levels, resulting in alterations in mitochondrial membrane potential and oxidative DNA damage in the cells. Upregulation of Bax/Caspase 3 protein expression and downregulation of Bcl-2 protein expression indicated the involvement of apoptotic pathways. Comprehensive analyses confirmed 35 starfish-derived anticancer compounds that inhibit cell proliferation, induce apoptosis, and target cancer-related pathways. Additionally, our study underscores the antioxidant potential of L. maculata starfish extracts, offering insights into marine organism-based therapies with promising medical applications.



中文翻译:

海星组织提取物的分子视角:针对人类癌 KB 细胞进行抗癌治疗

海洋环境富含天然生物活性化合物,包括斑马鱼和海星物种,它们因其卓越的组织再生能力而在药物研究中受到关注。尤其是斑马鱼,与人类的基因相似度高达 70% 左右。我们选择研究海星Luidia maculata,因为它具有卓越的组织再生能力和潜在的生物活性化合物,使其成为抗癌和抗氧化疗法的有希望的候选者。将人 KB 癌细胞置于斑L. maculata组织提取物中,使用 MTT 测试评估细胞毒性。通过 DCFH-DA 测量细胞内 ROS 水平,并使用 Rh-123 染色评估线粒体膜电位变化。通过彗星试验检测DNA氧化损伤,通过AO/EtBr双染色技术观察形态学凋亡变化。使用 HPLC、GC-MS/MS 和 FTIR 分析鉴定海星提取物中的活性化合物。从L. maculata 中提取的生物活性组分对 KB 癌细胞具有显着的抗增殖作用,诱导细胞凋亡。这些分数导致细胞内 ROS 水平显着增加,从而导致细胞内线粒体膜电位的改变和氧化 DNA 损伤。Bax/Caspase 3 蛋白表达的上调和 Bcl-2 蛋白表达的下调表明细胞凋亡途径的参与。综合分析证实,35 种海星衍生的抗癌化合物能够抑制细胞增殖、诱导细胞凋亡并靶向癌症相关途径。此外,我们的研究强调了斑斑海星提取物的抗氧化潜力,为基于海洋生物的疗法提供了具有前景的医疗应用的见解。

更新日期:2023-11-27
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