Department of Chemistry, College of Sciences and Arts, King Abdulaziz University, Rabigh, Saudi Arabia.
Marine Chemistry Department, Faculty of Marine Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
Nat Prod Res. 2023 Nov-Dec;37(24):4244-4250. doi: 10.1080/14786419.2023.2176489. Epub 2023 Feb 10.
This research aimed to investigate the anticancer properties of emestrin, a major constituent of ATCC 38163 through the induction of apoptosis in Huh-7 human hepatocellular carcinoma cells. In this study, this fungus was isolated from the fresh leaves of (Cham. & Schltdl.) C.A. Mey, and identified by morphology and 18S rDNA followed by large-scale fermentation in liquid biomalt broth medium. Epidithiodioxopiperazine derivative emestrin along with ten known metabolites were isolated and identified from the fungal extract. The cytotoxic assay revealed that emestrin had the strongest cytotoxicity against Huh-7 and A-549 cells with IC values of 4.89 and 6.3 μM, respectively. Using annexin V-FITC assay, treatment of Huh-7 cells with 4.89 µM for 24 h resulted in a significant increase in the percentage of early and late apoptosis (3.16% and 22.84%, respectively) compared to untreated cells. Additionally, Bax and bcl-2 protein levels were regulated, which induced apoptosis in treated cells. These results indicate that emestrin induces mitochondrial pathway to stimulate apoptosis and inhibits cell proliferation in hepatocellular carcinoma.
本研究旨在通过诱导 Huh-7 人肝癌细胞凋亡来研究 ATCC 38163 的主要成分 emestrin 的抗癌特性。在这项研究中，这种真菌是从（Cham. & Schltdl.）C.A. Mey 的新鲜叶子中分离出来的，并通过形态学和 18S rDNA 以及在液体麦芽肉汤培养基中进行大规模发酵进行了鉴定。从真菌提取物中分离并鉴定出了二硫二氧代哌嗪衍生物 emestrin 以及十种已知代谢物。细胞毒性测定表明，emestrin 对 Huh-7 和 A-549 细胞具有最强的细胞毒性，IC 值分别为 4.89 和 6.3μM。使用 Annexin V-FITC 测定法，用 4.89μM 的 emestrin 处理 Huh-7 细胞 24 小时后，与未处理的细胞相比，早期和晚期凋亡的细胞百分比显著增加（分别为 3.16%和 22.84%）。此外，Bax 和 bcl-2 蛋白水平受到调节，这诱导了处理细胞的凋亡。这些结果表明，emestrin 通过诱导线粒体途径刺激凋亡并抑制肝癌细胞增殖。
