Ginsenoside Rh2 inhibits breast cancer cell growth via<?A3B2 ACK?>ERβ-TNFα pathway

Ginsenoside Rh2 is one of rare panaxidiols extracted from Panax ginseng and a potential estrogen receptor ligand that exhibits moderate estrogenic activity. However, the effect of Rh2 on growth inhibition and its underlying molecular mechanism in human breast cells are not fully understood. In this...

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Main Authors: Peng Kunjian, Luo Tiao, Li Jijia, Huang Jingjia, Dong Zizeng, Liu Jia, Pi Chaoqiong, Zou Zizeng, Gu Qin, Liu Ousheng, Zhang Jian-Ting, Luo Zhi-Yong
Format: Article
Language:English
Published: China Science Publishing & Media Ltd. 2022-05-01
Series:Acta Biochimica et Biophysica Sinica
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Online Access:https://www.sciengine.com/doi/10.3724/abbs.2022039
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author Peng Kunjian
Luo Tiao
Li Jijia
Huang Jingjia
Dong Zizeng
Liu Jia
Pi Chaoqiong
Zou Zizeng
Gu Qin
Liu Ousheng
Zhang Jian-Ting
Luo Zhi-Yong
author_facet Peng Kunjian
Luo Tiao
Li Jijia
Huang Jingjia
Dong Zizeng
Liu Jia
Pi Chaoqiong
Zou Zizeng
Gu Qin
Liu Ousheng
Zhang Jian-Ting
Luo Zhi-Yong
author_sort Peng Kunjian
collection DOAJ
description Ginsenoside Rh2 is one of rare panaxidiols extracted from Panax ginseng and a potential estrogen receptor ligand that exhibits moderate estrogenic activity. However, the effect of Rh2 on growth inhibition and its underlying molecular mechanism in human breast cells are not fully understood. In this study, we tested cell viability by MTT and colony formation assays. Cell growth and cell cycle were determined to investigate the effect of ginsenoside Rh2 by flow cytometry. The expressions of estrogen receptors (ERs), TNFα, and apoptosis-related proteins were detected by qPCR and western blot analysis. The mechanisms of ERα and ERβ action were determined using transfection and inhibitors. Antitumor effect of ginsenoside Rh2 against MCF-7 cells was investigated in xenograft mice. Our results showed that ginsenoside Rh2 induced apoptosis and G1/S phase arrest in MCF-7 cells. Treatment of cells with ginsenoside Rh2 down-regulated protein levels of ERα, and up-regulated mRNA and protein levels of ERβ and TNFα. We also found that ginsenoside Rh2-induced TNFα over-expression is through up-regulation of ERβ initiated by ginsenoside Rh2. Furthermore, ginsenoside Rh2 induced MCF-7 cell apoptosis via estrogen receptor β-TNFα pathway in vivo. These results demonstrate that ginsenoside Rh2 promotes TNFα-induced apoptosis and G1/S phase arrest via regulation of ERβ.
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publisher China Science Publishing & Media Ltd.
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spelling doaj-art-feb6cdcb11ea49d89c74f23d1b34b97d2025-08-20T03:53:46ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452022-05-015464765610.3724/abbs.202203920d259ccGinsenoside Rh2 inhibits breast cancer cell growth via<?A3B2 ACK?>ERβ-TNFα pathwayPeng Kunjian0Luo Tiao1Li Jijia2Huang Jingjia3Dong Zizeng4Liu Jia5Pi Chaoqiong6Zou Zizeng7Gu Qin8Liu Ousheng9Zhang Jian-Ting10Luo Zhi-Yong11["Department of Biochemistry and Molecular Biology, Hunan Province Key Laboratory of Basic and Applied Hematology & Hunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha 410008, China"]["Hunan Key Laboratory of Oral Health Research & Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South University, Changsha 410008, China"]["Center of Stomatology, Xiangya Hospital, Central South University, Changsha 410008, China."]["Department of Biochemistry and Molecular Biology, Hunan Province Key Laboratory of Basic and Applied Hematology & Hunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha 410008, China"]["Department of Cell and Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA"]["Department of Biochemistry and Molecular Biology, Hunan Province Key Laboratory of Basic and Applied Hematology & Hunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha 410008, China"]["Department of Biochemistry and Molecular Biology, Hunan Province Key Laboratory of Basic and Applied Hematology & Hunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha 410008, China"]["Department of Biochemistry and Molecular Biology, Hunan Province Key Laboratory of Basic and Applied Hematology & Hunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha 410008, China"]["Department of Biochemistry and Molecular Biology, Hunan Province Key Laboratory of Basic and Applied Hematology & Hunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha 410008, China"]["Hunan Key Laboratory of Oral Health Research & Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South University, Changsha 410008, China"]["Department of Cell and Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA"]["Department of Biochemistry and Molecular Biology, Hunan Province Key Laboratory of Basic and Applied Hematology & Hunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha 410008, China"]Ginsenoside Rh2 is one of rare panaxidiols extracted from Panax ginseng and a potential estrogen receptor ligand that exhibits moderate estrogenic activity. However, the effect of Rh2 on growth inhibition and its underlying molecular mechanism in human breast cells are not fully understood. In this study, we tested cell viability by MTT and colony formation assays. Cell growth and cell cycle were determined to investigate the effect of ginsenoside Rh2 by flow cytometry. The expressions of estrogen receptors (ERs), TNFα, and apoptosis-related proteins were detected by qPCR and western blot analysis. The mechanisms of ERα and ERβ action were determined using transfection and inhibitors. Antitumor effect of ginsenoside Rh2 against MCF-7 cells was investigated in xenograft mice. Our results showed that ginsenoside Rh2 induced apoptosis and G1/S phase arrest in MCF-7 cells. Treatment of cells with ginsenoside Rh2 down-regulated protein levels of ERα, and up-regulated mRNA and protein levels of ERβ and TNFα. We also found that ginsenoside Rh2-induced TNFα over-expression is through up-regulation of ERβ initiated by ginsenoside Rh2. Furthermore, ginsenoside Rh2 induced MCF-7 cell apoptosis via estrogen receptor β-TNFα pathway in vivo. These results demonstrate that ginsenoside Rh2 promotes TNFα-induced apoptosis and G1/S phase arrest via regulation of ERβ.https://www.sciengine.com/doi/10.3724/abbs.2022039ginsenoside Rh2estrogen receptorTNFαbreast cancerapoptosis
spellingShingle Peng Kunjian
Luo Tiao
Li Jijia
Huang Jingjia
Dong Zizeng
Liu Jia
Pi Chaoqiong
Zou Zizeng
Gu Qin
Liu Ousheng
Zhang Jian-Ting
Luo Zhi-Yong
Ginsenoside Rh2 inhibits breast cancer cell growth via<?A3B2 ACK?>ERβ-TNFα pathway
Acta Biochimica et Biophysica Sinica
ginsenoside Rh2
estrogen receptor
TNFα
breast cancer
apoptosis
title Ginsenoside Rh2 inhibits breast cancer cell growth via<?A3B2 ACK?>ERβ-TNFα pathway
title_full Ginsenoside Rh2 inhibits breast cancer cell growth via<?A3B2 ACK?>ERβ-TNFα pathway
title_fullStr Ginsenoside Rh2 inhibits breast cancer cell growth via<?A3B2 ACK?>ERβ-TNFα pathway
title_full_unstemmed Ginsenoside Rh2 inhibits breast cancer cell growth via<?A3B2 ACK?>ERβ-TNFα pathway
title_short Ginsenoside Rh2 inhibits breast cancer cell growth via<?A3B2 ACK?>ERβ-TNFα pathway
title_sort ginsenoside rh2 inhibits breast cancer cell growth via a3b2 ack erβ tnfα pathway
topic ginsenoside Rh2
estrogen receptor
TNFα
breast cancer
apoptosis
url https://www.sciengine.com/doi/10.3724/abbs.2022039
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