Lipid-Soluble Ginseng Extract Induces Apoptosis and G0/G1 Cell Cycle Arrest in NCI-H460 Human Lung Cancer Cells

Abstract

This study was performed to elucidate the anticancer mechanism of a lipid-soluble ginseng extract (LSGE) by analyzing induction of apoptosis and arrest of cell cycle progression using the NCI-H460 human lung cancer cell line. Proliferation of NCI-H460 cells was potently inhibited by LSGE in a dose-dependent manner. The cell cycle arrest at the G0/G1 phase in NCI-H460 cells was induced by LSGE. The percentage of G0/G1 phase cells significantly increased, while that of S phase cells decreased after treatment with LSGE. The expression levels of cyclin-dependent kinase2 (CDK2), CDK4, CDK6, cyclin D3 and cyclin E related to G0/G1 cells progression were also altered by LSGE. In addition, LSGE-induced cell death occurred through apoptosis, which was accompanied by increasing the activity of caspases including caspase-8, caspase-9 and caspase-3. Consistent with enhancement of caspase activity, LSGE increased protein levels of cleaved caspase-3, caspase-8, caspase-9, and poly-ADP-ribose polymerase (PARP). These apoptotic effects of LSGE were inhibited by the pan-caspase inhibitor Z-VAD-fmk. These findings indicate that LSGE inhibits NCI-H460 human lung cancer cell growth by cell cycle arrest at the G0/G1 phase and induction of caspase-mediated apoptosis.

Lipid-Soluble Ginseng Extract Inhibits Invasion and Metastasis of B16F10 Melanoma Cells

“…8 For in vitro tests, LSGE was dissolved in dimethyl sulfoxide (DMSO) and further diluted with the culture media such that the final concentration of DMSO did not exceed 0.1%. 15 For in vivo tests, LSGE was dissolved in ethanol and further diluted in sterilized distilled water such that the final ethanol concentration was 4% before oral administration. 8,14 Proliferation assay B16F10 mouse melanoma cell line (American Type Culture Collection, Manassa, VA) was cultured in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum (FBS) and 100 lg/mL of streptomycin sulfate.…”

“…Cell proliferation assays were performed using an XTT (sodium 3 0 -[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis (4-methoxy-6-nitro) benzene sulfonic acid hydrate) Cell Proliferation Kit II (Roche, Indianapolis, IN) as previously described. 15 B16F10 cells were plated at 1 · 10 4 cells/well in 96-well culture plates, incubated overnight, and treated with 0.1% DMSO (vehicle control), 0.3, 1.0, 3.0, or 10.0 lg/mL of LSGE for 24 h. Then, a XTT labeling reagent and electron-coupling reagent were added to each well according to the manufacturer's instructions. After the mixtures were incubated for 2 h at 37°C, the formazan dye was measured at 490 and 650 nm using a microplate reader (Molecular Devices, Sunnyvale, CA).…”

“…7,8,14,15 In particular, the anticancer activity of ginseng was reported to originate mainly from lipid-soluble components. 7 Since LSGE contained a very small amount of ginsenosides and no polysaccharides, it was assumed that the antitumor effect of LSGE is due to nonpolar components such as polyacetylenes and polyphenolics.…”

“…7,8 Polyacetylenes containing panaxynol, panaxydol, and panaxytriol have been regarded as main components responsible for anticancer activity of LSGE. 13,15,16 The polyacetylene content of LSGE was considered to be between 2.38% and 6.88%, while panaxynol was identified as a dominant polyacetylene of LSGE. 8 In our previous reports, LSGE inhibited the growth of initial and advanced human lung tumors in murine xenografts models without any apparent toxicity.…”

Analysis of Nonpolar Components from Ginseng of Different Ages

“…In addition to linoleic, palmitic, oleic and linolenic fatty acids and principal sesquiterpene components [4,5], polyacetylenes including panaxytriol, falcarinol and ginsenoyne A-K are present in ginseng as typical diyne lipid components [1,[6][7][8]. Recent studies reported that the nonpolar components of ginseng have antioxidant, antimicrobial, antitumor and anti-obesity activities [9][10][11][12]. A compound having pharmacological activity (such as falcarinol) could be found among them [13].…”