Authors
Yunpeng Hu, Chen Li, Yiyao Cui
Published in
Pakistan journal of pharmaceutical sciences. Volume 39. Issue 12. Pages 3805-3813. Dec 01, 2026.
Abstract
Breast cancer (BC) remains a significant global health threat with complex pathogenesis often linked to chemotherapy resistance and inflammatory microenvironments. Histidine triad nucleotide-binding protein 2 (HINT2) is a mitochondrial protein involved in metabolism and immunity, but its specific role in BC and potential as a therapeutic target require further elucidation.
This study aimed to identify novel therapeutic targets for BC and evaluate the anti-tumor efficacy and molecular mechanisms of Albiflorin (Al), a natural monoterpene glycoside.
Proteomic profiling was performed on BC xenografts in nude mice to identify differentially expressed proteins. In-vivo and in-vitro models (MDA-MB-231 cells) were established to assess the effects of Al (20 mg/kg or 20 µM) on tumor growth, apoptosis and cytokine production. Molecular docking and co-immunoprecipitation (Co-IP) were used to investigate the interactions among HINT2, NLRP3 and Al.
HINT2 was significantly upregulated in BC tissues and identified as a primary pro-tumorigenic factor. Co-IP confirmed an endogenous interaction between HINT2 and NLRP3. Al exhibited strong binding affinity to HINT2 (-7.36 kcal/mol) and significantly suppressed tumor volume and weight. Furthermore, Al treatment downregulated the HINT2/NLRP3 axis, reduced inflammatory cytokines (IL-1β, IL-6, TNF-α) and promoted apoptosis by modulating Caspase-3, Bax and Bcl-2 levels.
Albiflorin suppresses BC progression by inhibiting the HINT2/NLRP3 signaling pathway, suggesting HINT2 is a viable biomarker and Al a promising therapeutic agent for BC treatment.
PMID:
42708783
Bibliographic data and abstract were imported from PubMed on 08 Sep 2026.
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