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.

Single-dose Toxicity of Water-soluble Ginseng Pharmacopuncture Injected Intramuscularly in Rats

“…It appears to have antioxidant and anti-carcinogenic effects [ 15 , 16 ]. In addition, we found that the enzymatic processing of ginseng saponin could increase the content of active constituents and enhance its anti-cancer activity, presumably because of the production of minor saponins, such as Rh1, Rg3, Compound K, and PPT constituents in ginseng saponin [ 10 , 11 ].…”

“…have been synthesized by using an enzyme treated technique. This increases absorption in patients lacking the body enzymes necessary to degrade ginseng, thus yielding superior efficacy [ 10 , 11 ]. However, low molecular weight ginsenosides in ginseng are not soluble in water, so we must use homogenized technology for make a water-soluble ginseng pharmacopuncture.…”

Modified Panax ginseng extract regulates autophagy by AMPK signaling in A549 human lung cancer cells

“…A total of 7 ginsenosides, including Rg1, Re, Rf, Rb1, Rc, Rb2 and F1, were present in the GBX. By contrast, 5 ginsenosides, including Rh1, Rg3(S), Rg3(R), compound K and Rh2, were exclusively detected in MRGX (6,10 Cell viability assay. Cells (5x10 3 /well) were placed in a 96-well plate.…”

“…The AVOs can be quantified based on the fact that the increase in the intensity of the red fluorescence is proportional to the degree of acidity (17). For the FACS analysis, A549 cells (5x10 6 ) were placed in a 100-mm culture dish and treated with 0, 50 or 100 µg/ml of MRGX. After a 48-h incubation, 1 µg/ml of AO was added, and the cells were incubated for 15 min at 37̊C, and then subjected to flow cytometry examination.…”

“…In addition, the chemical profiles of enzymatically modified ginseng extract were addressed by high-performance liquid chromatography (HPLC) compared to butanol extract as previously reported by us. Five ginsenosides, including Rh1, Rg3(S), Rg3(R), compound K and Rh2, were exclusively detected (6).…”