Berberine inhibits breast carcinoma proliferation and metastasis under hypoxic microenvironment involving gut microbiota and endogenous metabolites

• DOI: 10.1016/j.phrs.2023.106817
• Publication Date: 2023-06-12T16:53:09Z
• Authors: Yanfang Sun; QianQian Zhou; Fangming Chen; Xiaoyan Gao; Linjun Yang; Xiaoyan Jin; Michael Wink; Farukh S. Sharopov; Gautam Sethi
• Keywords: MTT assay; Metabolome

A potential role of berberine, a benzyl isoquinoline alkaloid, in cancer therapy is apparent. Its underlying mechanisms berberine against breast carcinoma under hypoxia have not been elucidated. We focused on the doubt how restrains vitro and vivo. molecular analysis microbiome via 16 S rDNA gene sequencing DNA from mouse faeces confirmed that abundances diversity gut microbiota were significantly altered 4T1/Luc mice with higher survival rate following treatment. metabolome liquid chromatography-mass spectrometer/mass spectrometer (LC-MS/MS) revealed regulated various endogenous metabolites, especially L-palmitoylcarnitine. Furthermore, cytotoxicity was investigated MDA-MB-231, MCF-7, 4T1 cells. In to simulate hypoxic environment, MTT assay showed inhibited proliferation cells IC50 values 4.14 ± 0.35 μM, 26.53 3.12 μM 11.62 1.44 respectively. Wound healing trans-well invasion studies migration RT-qPCR shed light reduced expression hypoxia-inducible factor-1α (HIF-1α) gene. Immunofluorescence western blot demonstrated decreased E-cadherin HIF-1α protein. Taken together, these results provide evidence efficiently suppresses growth metastasis microenvironment, highlighting as promising anti-neoplastic agent combat carcinoma.