Herbal Composition Inhibits Mitochondrial Oxidative Phosphorylation to Prevent HER2-Positive Breast Cancer and...

Area of Science:

• Oncology
• Pharmacology
• Biochemistry

Background:

• HER2-positive breast cancer is aggressive with few treatment options.
• Traditional Chinese medicine herbs show potential antitumor effects.
• SLC is a novel herbal composition with potential therapeutic benefits.

Purpose of the Study:

• To investigate the inhibitory effects of SLC on HER2-positive breast cancer.
• To elucidate the underlying mechanisms of SLC's action.
• To evaluate SLC's efficacy in preclinical models.

Main Methods:

• UPLC-Q/TOF-MS for compound identification.
• In vitro assays for cell proliferation, migration, and mitochondrial function.
• Western blot analysis for signaling pathway assessment.
• In vivo xenograft models for tumor growth evaluation.
• Molecular docking for active component identification.

Main Results:

• SLC inhibited proliferation, migration, and mitochondrial function by reducing glucose uptake and ATP production.
• SLC downregulated p-HER2/HER2, p-AKT/AKT, and p-ERK/ERK, inhibiting the HER2 pathway.
• SLC affected PDK1/PDHA1 and SIRT1/PGC-1α/NRF1/TFAM signaling, impacting oxidative phosphorylation.
• SLC repressed tumor growth in vivo; Monomethyl lithospermate was identified as a key component.

Conclusions:

• SLC demonstrates significant inhibitory effects against HER2-positive breast cancer.
• SLC acts through modulating mitochondrial oxidative phosphorylation and the HER2 signaling pathway.
• SLC presents a promising therapeutic strategy for HER2-positive breast cancer.