Cleistanthin A derivative disrupts autophagy and suppresses head and neck squamous cell carcinoma progression via targeted vacuolar ATPase.

ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) present a significant challenge due to its heterogeneity and limited treatment options, often resulting in severe side effects and poor survival rates with conventional chemoradiotherapy. Here, we investigated the anticancer activity of halogenated benzoate derivatives of cleistanthin A, ECDD-S16 and ECDD-S18, in HNSCC cells. Our findings revealed that ECDD-S18 exhibited remarkable cytotoxicity, surpassing that of cisplatin with minimal impact on normal and cisplatin-sensitive cells. Notably, ECDD-S18 induced apoptosis in a dose-dependent manner and effectively targeted vacuolar ATPase (V-ATPase), impairing lysosomal acidification. Intriguingly, ECDD-S18 inhibited autophagic flux, as evidenced by increased autophagosome but decreased autolysoso

SUBMITTER: Wongpan A 

PROVIDER: S-EPMC11439923 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature