Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam.
Int J Mol Sci. 2024 Oct 22;25(21):11368. doi: 10.3390/ijms252111368.
Lung cancer stands out as a leading cause of death among various cancer types, highlighting the urgent need for effective anticancer drugs and the discovery of new compounds with potent therapeutic properties. Natural sources, such as the genus, offer various bioactive compounds. Adunctin E (AE), a dihydrochalcone derived from , exhibited several pharmacological activities, and its potential as an anticancer agent remains largely unexplored. Thus, this study aimed to elucidate its apoptotic-inducing effect and identify its molecular targets. The network pharmacology analysis led to the identification of 71 potential targets of AE against lung cancer. Subsequent gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway enrichment analyses revealed the involvement of these targets in cancer-associated signaling pathways. Notably, HSP90AA1, MAPK1, and PIK3CA emerged as key players in apoptosis. In silico molecular docking and dynamic simulations suggested a strong and stable interaction between AE and HSP90AA1. In vitro experiments further confirmed a significant apoptotic-inducing effect of AE on lung cancer cell lines A549 and H460. Furthermore, immunoblot analysis exhibited a substantial decrease in HSP90AA1 levels in response to AE treatment. These findings support the potential anticancer activity of AE through the HSP90AA1 mechanism, underscoring its promise as a novel compound worthy of further research and development for anti-lung cancer therapy.
肺癌是各种癌症类型中导致死亡的主要原因，这突显了对有效抗癌药物的迫切需求，以及发现具有强大治疗特性的新化合物的必要性。天然来源，如 属，提供了各种具有生物活性的化合物。来自 的二氢查尔酮衍生物 Adunctin E（AE）具有多种药理活性，但其作为抗癌药物的潜力在很大程度上尚未得到探索。因此，本研究旨在阐明其诱导细胞凋亡的作用，并确定其分子靶标。网络药理学分析确定了 AE 针对肺癌的 71 个潜在靶标。随后的基因本体 (GO)、京都基因与基因组百科全书 (KEGG) 和反应网络分析揭示了这些靶标参与癌症相关信号通路。值得注意的是，HSP90AA1、MAPK1 和 PIK3CA 是细胞凋亡的关键参与者。计算机分子对接和动态模拟表明，AE 与 HSP90AA1 之间存在强烈而稳定的相互作用。体外实验进一步证实了 AE 对肺癌细胞系 A549 和 H460 具有显著的诱导细胞凋亡作用。此外，免疫印迹分析显示，AE 处理后 HSP90AA1 水平显著下降。这些发现支持了 AE 通过 HSP90AA1 机制的抗癌活性，突显了其作为一种有前途的新型化合物，值得进一步研究和开发用于抗肺癌治疗。
