AKT1-targeted proapoptotic activity of compound K in human breast cancer cells

다국어 초록 (Multilingual Abstract)

Background: Breast cancer is a severe disease and the second leading cause of cancer death in womenworldwide. To surmount this, various diagnosis and treatment options for breast cancer have beendeveloped. One of the most effective strategies for cancer treatment is to induce apoptosis using naturallyoccurring compounds. Compound K (CK) is a ginseng saponin metabolite generated by humanintestinal bacteria. CK has been studied for its cardioprotective, antiinflammatory, and liver-protectiveeffects; however, the role of CK in breast cancer is not fully understood.
Methods: To investigate the anticancer effects of CK in SKBR3 and MDA-MB-231 cells, cell viability assaysand flow cytometry analysis were used. In addition, the direct targets of CK anticancer activity wereidentified using immunoblotting analysis and overexpression experiments. Invasion, migration, andclonogenic assays were carried out to determine the effects of CK on cancer metastasis.
Results: CK-induced cell apoptosis in SKBR3 cells as determined through 3-(4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assays, propidium iodide (PI) and annexin V staining, and morphologicalchanges. CK increased the cleaved forms of caspase-7, caspase-8, and caspase-9, whereas the expressionof Bcl-2 was reduced by CK. In assays probing the cell survival pathway, CK activated only AKT1 and notAKT2. Moreover, CK inhibited breast cancer cell invasion, migration, and colony formation. Throughregulation of AKT1 activity, CK exerts anticancer effects by inducing apoptosis.
Conclusion: Our results suggest that CK could be used as a therapeutic compound for breast cancer.

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