Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, Uttar Pradesh, India; Jawaharlal Nehru University, New Delhi 110067, India.
Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, Uttar Pradesh, India.
Int J Biol Macromol. 2023 Dec 1;252:126328. doi: 10.1016/j.ijbiomac.2023.126328. Epub 2023 Aug 12.
Lung cancer is the most common and lethal cancer worldwide, yet there are no adequate and novel medications to control this illness. Previous reports suggested the potential of protein kinases to target lung cancer by regulating autophagy. This study establishes the role of aescin, a triterpenoid saponin, in targeting protein kinases responsible for lung cancer proliferation and mobility. The experimental data revealed that aescin significantly impedes lung cancer cell proliferation by downregulating protein kinases such as AKT, mTOR, MEK, and ERK. Downregulation of AKT-mTOR may promote a string of events inducing cytotoxic autophagy-mediated apoptosis in the presence of aescin. Besides, aescin decreases mobility and invasion by downregulating HIF-1α and VEGF gene expressions. Moreover, it successfully monitors EGFR gene expression, improves lung histology, and regulates biochemical parameters in a pre-clinical DEN-induced lung cancer model. Aescin was observed to be safe and non-toxic in both in silico toxicity predictions and ex vivo erythrocyte fragility assays. Hence, this study elucidates the molecular mechanism of aescin in targeting protein kinases and suggests that it could be a safer and more viable therapeutic agent for lung cancer treatment.
肺癌是全球最常见和最致命的癌症，但目前尚无足够和新颖的药物来控制这种疾病。先前的报告表明，蛋白激酶通过调节自噬可能成为治疗肺癌的潜在靶点。本研究确立了七叶皂苷作为一种三萜皂苷，在靶向负责肺癌增殖和迁移的蛋白激酶方面的作用。实验数据显示，七叶皂苷通过下调 AKT、mTOR、MEK 和 ERK 等蛋白激酶，显著抑制肺癌细胞的增殖。AKT-mTOR 的下调可能会在七叶皂苷存在的情况下引发一连串事件，诱导细胞毒性自噬介导的细胞凋亡。此外，七叶皂苷通过下调 HIF-1α 和 VEGF 基因表达来降低迁移和侵袭能力。此外，它还成功地监测了 EGFR 基因表达，改善了肺组织学，并调节了 DEN 诱导的肺癌模型中的生化参数。在计算机毒性预测和体外红细胞脆性测定中，七叶皂苷被观察到是安全且无毒的。因此，本研究阐明了七叶皂苷靶向蛋白激酶的分子机制，并表明它可能成为治疗肺癌更安全、更可行的治疗药物。
