Lalmuansangi C, Nghakliana Fanai, Sailo Hmingremhlua, Tochhawng Lalchhandami, Trivedi Amit Kumar, Kharat Kiran R, Vellingiri Balachandar, Kumar Nachimuthu Senthil, Siama Zothan
Department of Zoology, Mizoram University (a Central University), Aizawl, 796004, India.
Department of Botany, Mizoram University (a Central University), Aizawl, 796004, India.
Discov Oncol. 2025 Mar 31;16(1):429. doi: 10.1007/s12672-025-02138-6.
Stemona tuberosa is widely recognized for its traditional applications as an anti-cancer agent. This study aimed to assess the anti-cancer properties of S. tuberosa in human lung adenocarcinoma A549 cells. Among the various solvent extracts of S. tuberosa, the methanolic extract showed the highest toxicity against A549 cells. The S. tuberosa extract elicited cytotoxic effects and suppressed colony formation in A549 cells in a dose-dependent manner. S. tuberosa activity was further supported by AO/EtBr staining, increased caspase 3/6 activity, upregulation of pro-apoptotic genes, DNA damage, and elevated lipid peroxidation, with decreasing antioxidant levels. LC-MS analysis identified 80 predominant secondary metabolites in the methanolic extracts of S. tuberosa. A network pharmacology study identified SRC as the primary target of compounds identified from S. tuberosa. SRC protein is crucial for advancing lung cancer because of its function in cell proliferation, survival, and metastasis. Among the various compounds identified from S. tuberosa extract, 4-Azatricyclo [4.3.1.13,8] undecan-5-one (ADE) (- 10.88 kcal/mol) and Dihydro-normorphine, 3-desoxy- (DNY) (- 10.83 kcal/mol) exhibited notable binding affinities for SRC. Further analysis using molecular dynamics simulations (100 ns) validated the stability of SRC-ligand complexes, with RMSD of 1.8 and 2.2 Å for ADE and DNY, respectively, alongside the establishment of essential hydrogen bonds with pivotal residues, including ASP408, ALA403, and THR438. Finally, gmx._MMPBSA showed favourable ΔGbind values for ADE (- 15.06 ± 0.11 kcal/mol) and DNY (- 15.66 ± 0.25 kcal/mol), which highlights the significant potential of ADE and DNY as effective SRC inhibitors, suggesting S. tuberosa as a novel candidate for cancer therapy.
百部因其作为抗癌剂的传统应用而被广泛认可。本研究旨在评估百部在人肺腺癌A549细胞中的抗癌特性。在百部的各种溶剂提取物中，甲醇提取物对A549细胞表现出最高的毒性。百部提取物以剂量依赖的方式引发细胞毒性作用并抑制A549细胞中的集落形成。AO/EtBr染色、caspase 3/6活性增加、促凋亡基因上调、DNA损伤和脂质过氧化升高以及抗氧化水平降低进一步支持了百部的活性。LC-MS分析确定了百部甲醇提取物中的80种主要次生代谢产物。一项网络药理学研究确定SRC是从百部分离出的化合物的主要靶点。SRC蛋白因其在细胞增殖、存活和转移中的作用而对肺癌进展至关重要。在从百部提取物中鉴定出的各种化合物中，4-氮杂三环[4.3.1.13,8]十一烷-5-酮（ADE）（-10.88 kcal/mol）和二氢去甲吗啡，3-脱氧-（DNY）（-10.83 kcal/mol）对SRC表现出显著的结合亲和力。使用分子动力学模拟（100 ns）的进一步分析验证了SRC-配体复合物的稳定性，ADE和DNY的RMSD分别为1.8和2.2 Å，同时与关键残基（包括ASP408、ALA403和THR438）建立了重要的氢键。最后，gmx._MMPBSA显示ADE（-15.06±0.11 kcal/mol）和DNY（-15.66±0.25 kcal/mol）具有良好的ΔGbind值，这突出了ADE和DNY作为有效SRC抑制剂的巨大潜力，表明百部是癌症治疗的新候选药物。
