title: An enzymatically fortified ginseng extract inhibits proliferation and induces apoptosis of KATO3 human gastric cancer cells via modulation of Bax, mTOR, PKB and IκBα.
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.
authors.affiliation: Division of Life Science, Korea Basic Science Institute, Daejeon 305‑333, Republic of Korea.
authors.forename: Jeong-Won
authors.initials: JW
authors.lastname: Hwang
authors.affiliation: East‑West Cancer Center, Daejeon University, Daejeon 302‑120, Republic of Korea.
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Baek
authors.affiliation: Division of Life Science, Korea Basic Science Institute, Daejeon 305‑333, Republic of Korea.
authors.forename: Ik-Soon
authors.initials: IS
authors.lastname: Jang
authors.affiliation: Division of Life Science, Korea Basic Science Institute, Daejeon 305‑333, Republic of Korea.
authors.forename: Kyeong Eun
authors.initials: KE
authors.lastname: Yang
authors.affiliation: Division of Life Science, Korea Basic Science Institute, Daejeon 305‑333, Republic of Korea.
authors.forename: Dong-Gi
authors.initials: DG
authors.lastname: Lee
authors.affiliation: Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305‑764, Republic of Korea.
authors.forename: So-Jung
authors.initials: SJ
authors.lastname: Yoon
authors.affiliation: Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305‑764, Republic of Korea.
authors.forename: Jaerang
authors.initials: J
authors.lastname: Rho
authors.affiliation: East‑West Cancer Center, Daejeon University, Daejeon 302‑120, Republic of Korea.
authors.forename: Chong-Kwan
authors.initials: CK
authors.lastname: Cho
authors.affiliation: East‑West Cancer Center, Daejeon University, Daejeon 302‑120, Republic of Korea.
authors.forename: Yeon-Weol
authors.initials: YW
authors.lastname: Lee
authors.affiliation: Research Center of Pharmacopucture Medicine, Korean Pharmacopuncture Institute, Seoul 157‑200, Republic of Korea.
authors.forename: Ki-Rok
authors.initials: KR
authors.lastname: Kwon
authors.affiliation: East‑West Cancer Center, Daejeon University, Daejeon 302‑120, Republic of Korea.
authors.forename: Hwa-Seung
authors.initials: HS
authors.lastname: Yoo
authors.affiliation: Department of Life Science, Dongguk University Seoul, Seoul 100‑715, Republic of Korea.
authors.forename: Jung-Suk
authors.initials: JS
authors.lastname: Sung
authors.affiliation: Department of Immunology, College of Medicine, Keimyung University, Daegu 704‑701, Republic of Korea.
authors.forename: Shin
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Immunology, College of Medicine, Keimyung University, Daegu 704‑701, Republic of Korea.
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Molecular Medicine, College of Medicine, Keimyung University, Daegu 704‑701, Republic of Korea.
authors.forename: Byeong-Churl
authors.initials: BC
authors.lastname: Jang
authors.affiliation: Division of Life Science, Korea Basic Science Institute, Daejeon 305‑333, Republic of Korea.
authors.forename: Jong-Soon
authors.initials: JS
authors.lastname: Choi
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D036145:Ginsenosides / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D005894:Panax / Q000737:chemistry*; D010766:Phosphorylation; D053147:Plant Exudates / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D036145:Ginsenosides; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D053147:Plant Exudates; D051028:bcl-2-Associated X Protein; D000072000:NF-KappaB Inhibitor alpha; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases