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

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 standar...

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Main Authors: Jisun Oh, Hyo-Jin Yoon, Jeong-Hoon Jang, Do-Hee Kim, Young-Joon Surh
Format: Article
Language:English
Published: Elsevier 2019-07-01
Series:Journal of Ginseng Research
Online Access:http://www.sciencedirect.com/science/article/pii/S1226845317303561
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author Jisun Oh
Hyo-Jin Yoon
Jeong-Hoon Jang
Do-Hee Kim
Young-Joon Surh
author_facet Jisun Oh
Hyo-Jin Yoon
Jeong-Hoon Jang
Do-Hee Kim
Young-Joon Surh
author_sort Jisun Oh
collection DOAJ
description 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 CD44high/CD24low 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 CD44high/CD24low 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
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spelling doaj.art-bf63f87fcb1047a282977a77dfc560ae2022-12-22T00:47:52ZengElsevierJournal of Ginseng Research1226-84532019-07-01433421430The standardized Korean Red Ginseng extract and its ingredient ginsenoside Rg3 inhibit manifestation of breast cancer stem cell–like properties through modulation of self-renewal signalingJisun Oh0Hyo-Jin Yoon1Jeong-Hoon Jang2Do-Hee Kim3Young-Joon Surh4Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, Republic of KoreaTumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, Republic of KoreaTumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, Republic of KoreaDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of KoreaTumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University, Seoul, South Korea; Corresponding author. College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwank-gu, Seoul 08826, Republic of Korea.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 CD44high/CD24low 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 CD44high/CD24low 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-renewalhttp://www.sciencedirect.com/science/article/pii/S1226845317303561
spellingShingle Jisun Oh
Hyo-Jin Yoon
Jeong-Hoon Jang
Do-Hee Kim
Young-Joon Surh
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
Journal of Ginseng Research
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url http://www.sciencedirect.com/science/article/pii/S1226845317303561
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