关键词: Antitumor Incomplete autophagy Lysosomal acidification Non-small cell lung cancer α-Hederin

Mesh : Humans Carcinoma, Non-Small-Cell Lung / metabolism pathology drug therapy Lysosomes / metabolism drug effects Autophagy / drug effects Lung Neoplasms / metabolism pathology drug therapy Oleanolic Acid / analogs & derivatives pharmacology Saponins / pharmacology Cell Line, Tumor TOR Serine-Threonine Kinases / metabolism Autophagosomes / metabolism drug effects A549 Cells

来  源:   DOI:10.1038/s41598-024-63348-6   PDF(Pubmed)

Abstract:
Lung cancer is the most common oncological disease worldwide, with non-small cell lung cancer accounting for approximately 85% of lung cancer cases. α-Hederin is a monodesmosidic triterpenoid saponin isolated from the leaves of Hedera helix L. or Nigella sativa and has been extensively studied for its antitumor activity against a variety of tumor cells. It has been suggested that α-Hederin is a potential regulator of autophagy and has high promise for application. However, the specific mechanism and characteristics of α-Hederin in regulating autophagy are not well understood. In this study, we confirmed the potential of α-Hederin application in lung cancer treatment and comprehensively explored the mechanism and characteristics of α-Hederin in regulating autophagy in lung cancer cells. Our results suggest that α-Hederin is an incomplete autophagy inducer that targets mTOR to activate the classical autophagic pathway, inhibits lysosomal acidification without significantly affecting the processes of autophagosome transport, lysosome biogenesis, autophagosome and lysosome fusion, and finally leads to impaired autophagic flux and triggers autophagic damage in NSCLC.
摘要:
肺癌是全球最常见的肿瘤疾病,非小细胞肺癌约占肺癌病例的85%。α-Hederin是从HederahelixL.或Nigellasativa的叶子中分离出的一种单糖三萜皂苷,已对其对多种肿瘤细胞的抗肿瘤活性进行了广泛研究。有人认为α-Hederin是自噬的潜在调节剂,具有很高的应用前景。然而,关于α-Hederin调节自噬的具体机制和特征尚不清楚。在这项研究中,证实了α-Hederin在肺癌治疗中的应用潜力,并全面探讨了α-Hederin调控肺癌细胞自噬的机制和特点。我们的结果表明,α-Hederin是一种不完全的自噬诱导剂,靶向mTOR激活经典的自噬途径。抑制溶酶体酸化,而不会显着影响自噬体运输过程,溶酶体生物发生,自噬和溶酶体融合,并最终导致受损的自噬通量并引发NSCLC的自噬损伤。
公众号