Background There is a limited range of treatment options for triple-negative breast cancer (TNBC), a cancer known for its aggressiveness; therefore, innovative alternative therapies are required. A link between TNBC progression and bacterial dysbiosis in the gut microenvironment has been demonstrated. Thai traditional formulary medicine (TTFM), comprising bioactive natural products and medicinal plants, exhibits anti-cancer properties. However, the effectiveness of TTFM against breast cancer (BC) has not been clarified. The present study aimed to identify the secondary metabolites of TTFM and investigate its effects on BC both in vitro and in vivo. Methods The metabolite profiles of TTFM extracts were investigated using LC-MS/MS analysis. The anti-cancer activities were examined using a cell viability assay. The effects on the apoptosis pathway and gene expression profiles were also investigated using an apoptosis assay and RNA sequencing analysis. Next, TTFM extracts were examined in 4T1 xenografted mouse models. The gut microbiota profiles and tumor gene expression were investigated by 16S rDNA sequencing and nanoString, respectively. Results LC-MS/MS identified 302 compounds in the TTFM extract. In breast cancer cells, TTFM inhibited cell proliferation and induced apoptosis. Additionally, TTFM treatment partially restored the gut microbiota balance, increasing the abundance of Butyrivibrio hungatei and reducing Clostridium saccharolyticum. NanoString analysis showed that TTFM modulated immune responses by upregulating the Pias1 gene and downregulating pro-inflammatory cytokines (IL-1r2, IL-1β, IL-2) and cancer-related genes (Ccno, Nkd1). Conclusion This study highlights the anti-cancer potential of TTFM extracts, suggesting its future use in the development of novel therapeutic strategies for breast cancer.
Khamwut et al. (Mon,) studied this question.