An enzymatically fortified ginseng extract inhibits proliferation and induces apoptosis of KATO3 human gastric cancer cells via modulation of Bax, mTOR, PKB and IκBα

Hwang,Jeong‑Won; Baek,Young‑Mi; Jang,Ik‑Soon; Yang,Kyeong  Eun; Lee,Dong‑Gi; Yoon,So‑Jung; Rho,Jaerang; Cho,Chong‑Kwan; Lee,Yeon‑Weol; Kwon,Ki‑Rok; Yoo,Hwa‑Seung; Sung,Jung‑Suk; Kim,Shin; Park,Jong‑Wook; Jang,Byeong‑Churl; Choi,Jong‑Soon

doi:10.3892/mmr.2014.2704

An enzymatically fortified ginseng extract inhibits proliferation and induces apoptosis of KATO3 human gastric cancer cells via modulation of Bax, mTOR, PKB and IκBα

Authors:
- Jeong‑Won Hwang
- Young‑Mi Baek
- Ik‑Soon Jang
- Kyeong Eun Yang
- Dong‑Gi Lee
- So‑Jung Yoon
- Jaerang Rho
- Chong‑Kwan Cho
- Yeon‑Weol Lee
- Ki‑Rok Kwon
- Hwa‑Seung Yoo
- Jung‑Suk Sung
- Shin Kim
- Jong‑Wook Park
- Byeong‑Churl Jang
- Jong‑Soon Choi
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Affiliations: Division of Life Science, Korea Basic Science Institute, Daejeon 305‑333, Republic of Korea, East‑West Cancer Center, Daejeon University, Daejeon 302‑120, Republic of Korea, Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305‑764, Republic of Korea, Research Center of Pharmacopucture Medicine, Korean Pharmacopuncture Institute, Seoul 157‑200, Republic of Korea, Department of Life Science, Dongguk University Seoul, Seoul 100‑715, Republic of Korea, Department of Immunology, College of Medicine, Keimyung University, Daegu 704‑701, Republic of Korea, Department of Molecular Medicine, College of Medicine, Keimyung University, Daegu 704‑701, Republic of Korea
Published online on: October 20, 2014 https://doi.org/10.3892/mmr.2014.2704
Pages: 670-676

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Abstract

Accumulative evidence suggests ginseng extract and/or its major components, ginsenosides and compound K, a metabolized ginseng saponin, have anti‑cancer effects. In the present study, the effects of a ginseng butanolic extract (GBX) and an enzymatically fortified ginseng extract (FGX), with enriched ginsenosides and compound K, on the growth of KATO3 human gastric cancer cells were investigated using a cell viability assay. While treatment with GBX at 31.25‑125 mg/ml for 24 h did not affect the proliferation of KATO3 cells, FGX under the same conditions inhibited cell proliferation in a concentration‑dependent manner. Furthermore, Annexin V/PI-staining and flow cytometric analysis demonstrated that the population of apoptotic KATO3 cells was increased following treatment with FGX, which was greater than in the GBX‑treated cells, suggesting that FGX had a stronger apoptotic effect than GBX. To investigate the underlying mechanism of the cytostatic and cytotoxic effects of the ginseng extracts, apoptosis-associated proteins were assessed using western blot analysis. The data revealed higher expression levels of B-cell lymphoma 2-associated X protein (Bax), lower expression of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor α (IκBα) and reduced phosphorylation of mammalian target of rapamycin (mTOR) and protein kinase B (PKB) in the FGX‑treated KATO3 cells than in the GBX‑treated cells. Collectively, these results demonstrated for the first time, to the best of our knowledge, that FGX had stronger anti‑proliferative and pro‑apoptotic effects on KATO3 cells than GBX. The anti‑proliferative and/or pro‑apoptotic effects of FGX appeared to be mediated via the upregulation of Bax, IκBα proteolysis (activation of nuclear factor‑κB) and the blocking of mTOR and PKB signals.

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