To evaluate a novel
therapy for
triple-negative breast cancer (TNBC), the biological responses to
vitamin K3 (VK3) should be considered with the understanding of the features of
breast cancer. In human
breast cancer cell lines, the effects of VK3 on cell growth inhibition and the cellular signaling pathway were determined by MTT assay and western blotting. In the in vivo study, a subcutaneous
tumor model of
breast cancer was created, VK3 was injected into the subcutaneous
tumors, and
tumor size was measured. The IC50 of VK3 for
breast cancer cells was calculated to be 11.3-25.1 µM. VK3 induced phosphorylation of whole
tyrosine and
epidermal growth factor receptor. VK3 mediated phosphorylation of
extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal
kinase (JNK) for 30 min. ERK but not JNK phosphorylation was maintained for at least 6 h. In contrast, another
antioxidant agent,
catalase, showed no effect on either ERK phosphorylation or growth inhibition. On built-up
tumors under the skin of mice, local treatment with VK3 was effective in a time- and dose-dependent manner, and the experiments for total
tumor volume also showed a dose-dependent effect of VK3. The expression of phosphorylated ERK was clearly detected at 10.9 times the control in
tumor tissue, whereas
ethanol itself showed no effect. In conclusion, ERK plays a critical role in VK3-induced growth inhibition, and it will be the focus of next steps in the development of molecular
therapy for TNBC.