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KMID : 0352720180420040562
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Journal of Ginseng Research
2018 Volume.42 No. 4 p.562 ~ p.570
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Bioactivity-guided isolation of ginsenosides from Korean Red Ginseng with cytotoxic activity against human lung adenocarcinoma cells
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Yu Jae-Sik
Roh Hyun-Soo
Baek Kwan-Hyuck
Lee Seul
Kim Sil
So Hae-Min
Moon Eun-Jung
Pang Chang-Hyun
Jang Tae-Su
Kim Ki-Hyun
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Abstract
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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 transferaseemediated 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 acetatee 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 activityagainst all human lung cancer cell lines examined,withIC50 values ranging from161.1 mMto 264.6 mM. The cytotoxicity of ginsenoside Rg3 was found to be mediated by induction of apoptosis in a caspaseindependent manner. These findings provide experimental evidence for a novel biological activity of ginsenoside Rg3 against human lung cancer cells.
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KEYWORD
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Apoptosis, Cytotoxicity, Ginsenoside Rg3, Korean Red Ginseng, Lung cancer
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