The Antitumor Role of Incomptine A in a Breast Cancer Murine Model: Impairment of Hexokinase II Expression and Apoptosis Induction.

Breast cancer (BC) is the most common type of cancer in women worldwide. Hexokinase II (HKII) overexpression is associated with the proliferation and survival of tumor cells, as it inhibits apoptosis. Incomptine A (IA) is cytotoxic to breast cancer cells, likely due to a decrease in the expression of HKII. This study evaluated the antitumor activity of IA in an in vivo mouse model of BC. A model was generated from 4T1 cells and grouped tumor-bearing animals according to treatment: in IA or doxorubicin (DOXO), or untreated (UT). Comparing the body weight and tumor size between groups, tumors were analyzed using histopathological, Western blot, flow cytometry, and mitochondrial activity assays. Tumors IA-treated showed a reduction in size, weight, and number of tumor cells; the expression of HKII and Bcl-2 decreased, while that of Caspase-3 increased. IA treatment increased apoptosis and reduced mitochondrial activity in tumor cells. This data showed that IA has an impact on tumor cells by reducing tumor volume and size, increasing cell apoptosis, and decreasing mitochondrial activity, all of which could be attributed to reduced HKII expression. Therefore, IA may be a promising compound that requires further studies to elucidate its mechanism of action and analyze its possible future use in BC.