ArticleJournal of ginseng research2017
Induction of Forkhead Class box O3a and apoptosis by a standardized ginsenoside formulation, KG-135, is potentiated by autophagy blockade in A549 human lung cancer cells.
Article in Journal of ginseng research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 29 citations in OpenAlex.
- Repurposing Antimalarials for Oral Cancer: Selective Efficacy of Hydroxychloroquine on Gingival Squamous Cell Carcinoma.International journal of molecular sciences · 2025Article
- Ginsenoside Rb1 Inhibits the Proliferation of Lung Cancer Cells by Inducing the Mitochondrial-mediated Apoptosis Pathway.Anti-cancer agents in medicinal chemistry · 2024Article
- Protective effects of Gypenoside XVII against cerebral ischemia/reperfusion injury via SIRT1-FOXO3A- and Hif1a-BNIP3-mediated mitochondrial autophagy.Journal of translational medicine · 2022Article
- A Novel Analysis Method for Simultaneous Determination of 31 Pesticides by High-Performance Liquid Chromatography-Tandem Mass Spectrometry in Ginseng.Journal of analytical methods in chemistry · 2022Article
- Transformation Mechanism of Rare Ginsenosides in American Ginseng by Different Processing Methods and Antitumour Effects.Frontiers in nutrition · 2022Article
- Pharmacological potential of ginseng and its major component ginsenosides.Journal of ginseng research · 2021Review
- Inhibition of autophagy of Cajal mesenchymal cells by gavage of tong bian decoction based on the rat model of chronic transit constipation.Saudi journal of biological sciences · 2020Article
- Targeting off-target effects: endoplasmic reticulum stress and autophagy as effective strategies to enhance temozolomide treatment.OncoTargets and therapy · 2019Review
- Lignan Glycosides and Flavonoid Glycosides from the Aerial Portion ofMolecules (Basel, Switzerland) · 2018Article
- Cytoprotective Effect of Epigallocatechin Gallate (EGCG)-5'-O-α-Glucopyranoside, a Novel EGCG Derivative.International journal of molecular sciences · 2018Article
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundKG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5 ginsenosides, has been shown to inhibit various types of cancer cells; however, the underlying mechanisms are not fully understood. In this study, we explored its effects in A549 human lung cancer cells to investigate the induction of Forkhead Class box O3a (FOXO3a) and autophagy.
methodsCell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry. The changes of protein levels were determined using Western blot analysis. Autophagy induction was monitored by the formation of acidic vesicular organelles stained with acridine orange.
resultsKG-135 effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles without an increase of the upstream marker Beclin-1. Unconventionally, the autophagy adaptor protein p62 (sequestosome 1) was increased rather than decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as the cleavage of caspase-9, were also drastically enhanced, resulting in massive apoptosis.
conclusionBesides arresting the cells in G1 phase, KG-135 increased FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135-activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic pathways were potentiated by blockade of autophagy. Combination of KG-135 and autophagy inhibitor may be a novel strategy as an integrative treatment for cancers.
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