Hongwu mixture exerts inhibition on triple-negative breast cancer by regulating SAV1/Hippo signaling through ZNF143

Hongwu mixture (HWM) consists of Taxus chinensis, Marsdenia tenacissima, Rhizoma Curcumae, and Semen coicis. The objective of this study was to ascertain the potential role of the Hongwu mixture (HWM) in the treatment of triple-negative breast cancer (TNBC). TNBC cells were treated with low, medium, and high doses of HWM, and CCK-8 assays were conducted to evaluate the impact of different doses of HWM on TNBC cell viability. The target molecules of HWM were predicted using RNA-sequencing, and molecular docking models between HWM components and target proteins were developed. As the dose of HWM increased, TNBC cell viability gradually decreased. HWM inhibited the proliferation and mobility of TNBC cells, slowed the tumor growth, and upregulated the apoptosis of TNBC cells. HWM promoted Zinc finger protein 143 (ZNF143)-mediated transcriptional activation of salvador family WW domain-containing protein 1 (SAV1) by stabilizing ZNF143 protein expression, leading to phosphorylation of large tumor suppressor homolog 1 (LATS1) and Yes-associated protein 1 (YAP1). Knockdown of ZNF143/SAV1 signaling impaired the therapeutic effect of HWM, and treatment with verteporfin, pharmacological inhibition of YAP/TAZ, reversed the effects of knockdown of SAV1. Therefore, HWM might offer a potent strategy for managing TNBC effectively.