Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Bioactivity-guided isolation of ginsenosides from Korean Red Ginseng with cytotoxic activity against human lung adenocarcinoma cells

  • Yu, Jae Sik (School of Pharmacy, Sungkyunkwan University) ;
  • Roh, Hyun-Soo (Department of Molecular and Cellular Biology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Baek, Kwan-Hyuck (Department of Molecular and Cellular Biology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Seul (Department of Molecular and Cellular Biology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Sil (School of Pharmacy, Sungkyunkwan University) ;
  • So, Hae Min (School of Pharmacy, Sungkyunkwan University) ;
  • Moon, Eunjung (Charmzone R&D Center, Charmzone Co. LTD.) ;
  • Pang, Changhyun (School of Chemical Engineering, Sungkyunkwan University) ;
  • Jang, Tae Su (Institute of Green Bio Science & Technology, Seoul National University) ;
  • Kim, Ki Hyun (School of Pharmacy, Sungkyunkwan University)
  • Received : 2017.11.26
  • Accepted : 2018.02.08
  • Published : 2018.10.15
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Abstract

Background: Lung cancer is the leading cause of cancer-related death worldwide. In this study, we used a bioactivity-guided isolation technique to identify constituents of Korean Red Ginseng (KRG) with antiproliferative activity against human lung adenocarcinoma cells. Methods: Bioactivity-guided fractionation and preparative/semipreparative HPLC purification were used with LC/MS analysis to separate the bioactive constituents. Cell viability and apoptosis in human lung cancer cell lines (A549, H1264, H1299, and Calu-6) after treatment with KRG extract fractions and constituents thereof were assessed using the water-soluble tetrazolium salt (WST-1) assay and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, respectively. Caspase activation was assessed by detecting its surrogate marker, cleaved poly adenosine diphosphate (ADP-ribose) polymerase, using an immunoblot assay. The expression and subcellular localization of apoptosis-inducing factor were assessed using immunoblotting and immunofluorescence, respectively. Results and conclusion: Bioactivity-guided fractionation of the KRG extract revealed that its ethyl acetate-soluble fraction exerts significant cytotoxic activity against all human lung cancer cell lines tested by inducing apoptosis. Chemical investigation of the ethyl acetatesoluble fraction led to the isolation of six ginsenosides, including ginsenoside Rb1 (1), ginsenoside Rb2 (2), ginsenoside Rc (3), ginsenoside Rd (4), ginsenoside Rg1 (5), and ginsenoside Rg3 (6). Among the isolated ginsenosides, ginsenoside Rg3 exhibited the most cytotoxic activity against all human lung cancer cell lines examined, with $IC_{50}$ values ranging from $161.1{\mu}M$ to $264.6{\mu}M$. The cytotoxicity of ginsenoside Rg3 was found to be mediated by induction of apoptosis in a caspase-independent manner. These findings provide experimental evidence for a novel biological activity of ginsenoside Rg3 against human lung cancer cells.

Keywords

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