Cleistanthin A derivative disrupts autophagy and suppresses head and neck squamous cell carcinoma progression via targeted vacuolar ATPase
Issued Date
2024-09-29
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85205335378
Pubmed ID
39343784
Journal Title
Scientific reports
Volume
14
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific reports Vol.14 No.1 (2024) , 22582
Suggested Citation
Wongpan A., Panvongsa W., Krobthong S., Nutho B., Kanjanasirirat P., Jearawuttanakul K., Khumpanied T., Phlaetita S., Chabang N., Munyoo B., Tuchinda P., Ponpuak M., Borwornpinyo S., Chairoungdua A. Cleistanthin A derivative disrupts autophagy and suppresses head and neck squamous cell carcinoma progression via targeted vacuolar ATPase. Scientific reports Vol.14 No.1 (2024) , 22582. doi:10.1038/s41598-024-73186-1 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/101509
Title
Cleistanthin A derivative disrupts autophagy and suppresses head and neck squamous cell carcinoma progression via targeted vacuolar ATPase
Corresponding Author(s)
Other Contributor(s)
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 autolysosome formation. Furthermore, proteomic analysis demonstrated downregulation of cathepsin D (CTSD), the lysosomal protease in ECDD-S18-treated HNSCC cells, concurrent with suppressed cell migration. ECDD-S18 also decreased expression of mesenchymal markers, suggesting inhibition of epithelial-mesenchymal transition (EMT). Importantly, cotreatment with ECDD-S18 and cisplatin enhanced the reduction in cell viability. Collectively, our results indicated that the anticancer activity of ECDD-S18 partly stems from its ability to disrupt lysosomal acidification and inhibit autophagy via targeted inhibition of V-ATPase. These findings underscore the therapeutic promise of ECDD-S18 in HNSCC treatment, either alone or in combination with existing drugs, while mitigating toxicity to normal cells.
