The standardized Korean Red Ginseng extract and its ingredient ginsenoside Rg3 inhibit manifestation of breast cancer stem cell-like properties through modulation of self-renewal signaling

Jisun Oh; Hyo-Jin Yoon; Jeong-Hoon Jang; Do-Hee Kim; Young-Joon Surh

doi:10.1016/j.jgr.2018.05.004

The standardized Korean Red Ginseng extract and its ingredient ginsenoside Rg3 inhibit manifestation of breast cancer stem cell-like properties through modulation of self-renewal signaling

J Ginseng Res. 2019 Jul;43(3):421-430. doi: 10.1016/j.jgr.2018.05.004. Epub 2018 May 17.

Authors

Jisun Oh¹, Hyo-Jin Yoon¹, Jeong-Hoon Jang¹, Do-Hee Kim², Young-Joon Surh^{1

2

3}

Affiliations

¹ Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
² Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
³ Cancer Research Institute, Seoul National University, Seoul, South Korea.

Abstract

Background: The ginsenoside Rg3, one of active components of red ginseng, has chemopreventive and anticancer potential. Cancer stem cells retain self-renewal properties which account for cancer recurrence and resistance to anticancer therapy. In our present study, we investigated whether the standardized Korean Red Ginseng extract (RGE) and Rg3 could modulate the manifestation of breast cancer stem cell-like features through regulation of self-renewal activity.

Methods: The effects of RGE and Rg3 on the proportion of CD44^high/CD24^low cells, as representative characteristics of stem-like breast cancer cells, were determined by flow cytometry. The mammosphere formation assay was performed to assess self-renewal capacities of breast cancer cells. Aldehyde dehydrogenase activity of MCF-7 mammospheres was measured by the ALDEFLUOR assay. The expression levels of Sox-2, Bmi-1, and P-Akt and the nuclear localization of hypoxia inducible factor-1α in MCF-7 mammospheres were verified by immunoblot analysis.

Results: Both RGE and Rg3 decreased the viability of breast cancer cells and significantly reduced the populations of CD44^high/CD24^low in MDA-MB-231 cells. RGE and Rg3 treatment attenuated the expression of Sox-2 and Bmi-1 by inhibiting the nuclear localization of hypoxia inducible factor-1α in MCF-7 mammospheres. Suppression of the manifestation of breast cancer stem cell-like properties by Rg3 was mediated through the blockade of Akt-mediated self-renewal signaling.

Conclusion: This study suggests that Rg3 has a therapeutic potential targeting breast cancer stem cells.

Keywords: Breast cancer stem cells; Ginseng; Ginsenoside Rg3; Red ginseng extract; Self-renewal.