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Inhibition of Autophagy by Berbamine Hydrochloride Mitigates Tumor Immune Escape by Elevating MHC-I in Melanoma Cells

Published:13 September 2024 DOI: 10.3390/cells13181537
Jinhuan Xian, Leilei Gao, Zhenyang Ren, Yanjun Jiang, Junjun Pan, Zheng Ying, Zhenyuan Guo, Qingsong Du, Xu Zhao, He Jin, Hua Yi, Jieying Guan, Shan Hu

Abstract

Impaired tumor cell antigen presentation contributes significantly to immune evasion. This study identifies Berbamine hydrochloride (Ber), a compound derived from traditional Chinese medicine, as an effective inhibitor of autophagy that enhances antigen presentation in tumor cells. Ber increases MHC-I-mediated antigen presentation in melanoma cells, improving recognition and elimination by CD8+ T cells. Mutation of Atg4b, which blocks autophagy, also raises MHC-I levels on the cell surface, and further treatment with Ber under these conditions does not increase MHC-I, indicating Ber’s role in blocking autophagy to enhance MHC-I expression. Additionally, Ber treatment leads to the accumulation of autophagosomes, with elevated levels of LC3-II and p62, suggesting a disrupted autophagic flux. Fluorescence staining and co-localization analyses reveal that Ber likely inhibits lysosomal acidification without hindering autophagosome–lysosome fusion. Importantly, Ber treatment suppresses melanoma growth in mice and enhances CD8+ T cell infiltration, supporting its therapeutic potential. Our findings demonstrate that Ber disturbs late-stage autophagic flux through abnormal lysosomal acidification, enhancing MHC-I-mediated antigen presentation and curtailing tumor immune escape.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
BERBAMINE DIHYDROCHLORIDE 6078-17-7 C37H42Cl2N2O5 241 suppliers $19.00-$1729.50
BERBAMINE DIHYDROCHLORIDE 6078-17-7 C37H42Cl2N2O5 241 suppliers $19.00-$1729.50
BERBAMINE DIHYDROCHLORIDE 6078-17-7 C37H42Cl2N2O5 241 suppliers $19.00-$1729.50
BERBAMINE DIHYDROCHLORIDE 6078-17-7 C37H42Cl2N2O5 241 suppliers $19.00-$1729.50

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