Dammarane-type triterpene ginsenoside-Rg18 inhibits human non-small cell lung cancer A549 cell proliferation via G1 phase arrest

Abstract

Abstract.A previous study reported that a novel dammarane-type triterpene saponin, ginsenoside-Rg18, derived from the root of Panax ginseng, displayed hydroxyl radical scavenging, anti-bacterial and cytotoxic activities. However, the underlying molecular mechanisms of its anti-proliferative effect on non-small cell lung cancer (NSCLC) A549 cells remains unclear. In the present study, it was determined that Rg18 inhibited the proliferation of A549 cells with a half-maximal inhibitory concentration of 150 µM. Flow cytometry analysis indicated that cell cycle progression was blocked by Rg18 at G 1 phase in A549 cells, which was accompanied by downregulation of cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, cyclin D1, cyclin D2, cyclin E and phosphorylated retinoblastoma protein expression at the protein level. In addition, the CDK inhibitors (CDKNs), CDKN1A and CDKN1B, were upregulated following Rg18 treatment. Furthermore, Rg18 treatment resulted in the intracellular accumulation of reactive oxygen species (ROS), and a dose-dependent inhibition of p38 mitogen activated protein kinase (p38), c-Jun N-terminal kinase (JNK) and nuclear factor-κB (NF-κB)/p65 phosphorylation. Taken together, Rg18-mediated G 1 phase arrest was closely associated with the generation of intracellular ROS, and p38, JNK and NF-κB/p65 inhibition in A549 human NSCLC cells.

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

“…F. H. Chen, Panax ginseng and Cinnamomum cassia Presl., with various biological effects including anti-oxidative, anti-inflammatory, and anti-cancer activities [219][220][221][222]. Ginsenosides mainly exert anti-cancer effects in colorectal, breast, liver and lung cancers, through inhibiting cell proliferation and migration, angiogenesis, and reversing drug resistance [7,[223][224][225][226][227][228][229][230]. Ginsenoside Rg3, ginsenoside Rh2, and compound K are the primary bioactive compounds among ginsenosides for cancer prevention.…”

Therapeutic Potential of Ginsenosides as an Adjuvant Treatment for Diabetes

“…Recent studies have shown that ginsenosides can be used to treat early chronic kidney disease (Xu et al, 2017 ), non-small-cell lung cancer (Leem et al, 2018 ), septic acute lung injury and acute respiratory distress syndrome (Sun et al, 2015 ). A randomized controlled trial showed that ginsenoside Rb1 ameliorates the renal function of patients with early chronic kidney disease.…”

Characterization of a Novel Ginsenoside MT1 Produced by an Enzymatic Transrhamnosylation of Protopanaxatriol-Type Ginsenosides Re

“…A similar ginsenoside-ginsenoside Rg 18 (Figure S1), which differs from MT1 in that it is linked to an additional glucose moiety at the C-6 position-was recently found, isolated and characterized from Panax ginseng roots [33]. Rg 18 has been shown to have various important pharmacological effects, such as anticancer [34] and neuroprotective effects [35]. However, the content of Rg 18 in ginseng is <36.0 µg/g of ginseng, which means that its application is limited by its scarcity in plants.…”