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

Journal of Ginseng Research 2019년 43권 4호 p.692 ~ 698
 ( Choi Eun-Ju ) - Sungkyunkwan University Department of Integrative Biotechnology

 ( Kim Eun-Ji ) - Sungkyunkwan University Department of Integrative Biotechnology
 ( Kim Ji-Hye ) - Sungkyunkwan University Department of Integrative Biotechnology
 ( Yoon Kee-Jung ) - Sungkyunkwan University Department of Integrative Biotechnology
 ( Kim Sung-Gyu ) - Sungkyunkwan University Research and Business Foundation
 ( Lee Jong-Sung ) - Sungkyunkwan University Department of Integrative Biotechnology
 ( Cho Jae-Youl ) - Sungkyunkwan University Department of Integrative Biotechnology

Abstract


Background: Breast cancer is a severe disease and the second leading cause of cancer death in women worldwide. To surmount this, various diagnosis and treatment options for breast cancer have been developed. One of the most effective strategies for cancer treatment is to induce apoptosis using naturally occurring compounds. Compound K (CK) is a ginseng saponin metabolite generated by human intestinal bacteria. CK has been studied for its cardioprotective, antiinflammatory, and liver-protective effects; 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 assays and flow cytometry analysis were used. In addition, the direct targets of CK anticancer activity were identified using immunoblotting analysis and overexpression experiments. Invasion, migration, and clonogenic 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 morphological changes. CK increased the cleaved forms of caspase-7, caspase-8, and caspase-9, whereas the expression of Bcl-2 was reduced by CK. In assays probing the cell survival pathway, CK activated only AKT1 and not AKT2. Moreover, CK inhibited breast cancer cell invasion, migration, and colony formation. Through regulation 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.

키워드

AKT1; Apoptosis; Cancer; Compound K; Panax ginseng
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