PMID- 30337817 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230928 IS - 1226-8453 (Print) IS - 2093-4947 (Electronic) IS - 1226-8453 (Linking) VI - 42 IP - 4 DP - 2018 Oct TI - Bioactivity-guided isolation of ginsenosides from Korean Red Ginseng with cytotoxic activity against human lung adenocarcinoma cells. PG - 562-570 LID - 10.1016/j.jgr.2018.02.004 [doi] AB - 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 muM to 264.6 muM. 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. FAU - Yu, Jae Sik AU - Yu JS AD - School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea. FAU - Roh, Hyun-Soo AU - Roh HS AD - Department of Molecular and Cellular Biology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea. FAU - Baek, Kwan-Hyuck AU - Baek KH AD - Department of Molecular and Cellular Biology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea. FAU - Lee, Seul AU - Lee S AD - Department of Molecular and Cellular Biology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea. FAU - Kim, Sil AU - Kim S AD - School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea. FAU - So, Hae Min AU - So HM AD - School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea. FAU - Moon, Eunjung AU - Moon E AD - Charmzone R&D Center, Charmzone Co. LTD., Seoul, Republic of Korea. FAU - Pang, Changhyun AU - Pang C AD - School of Chemical Engineering, Sungkyunkwan University, Suwon, Republic of Korea. FAU - Jang, Tae Su AU - Jang TS AD - Institute of Green Bio Science & Technology, Seoul National University, Pyeong Chang, Republic of Korea. FAU - Kim, Ki Hyun AU - Kim KH AD - School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea. LA - eng PT - Journal Article DEP - 20180216 PL - Korea (South) TA - J Ginseng Res JT - Journal of ginseng research JID - 100890690 PMC - PMC6190500 OTO - NOTNLM OT - Apoptosis OT - Cytotoxicity OT - Ginsenoside Rg3 OT - Korean Red Ginseng OT - Lung cancer EDAT- 2018/10/20 06:00 MHDA- 2018/10/20 06:01 PMCR- 2018/02/16 CRDT- 2018/10/20 06:00 PHST- 2017/11/26 00:00 [received] PHST- 2018/01/31 00:00 [revised] PHST- 2018/02/08 00:00 [accepted] PHST- 2018/10/20 06:00 [entrez] PHST- 2018/10/20 06:00 [pubmed] PHST- 2018/10/20 06:01 [medline] PHST- 2018/02/16 00:00 [pmc-release] AID - S1226-8453(17)30350-0 [pii] AID - 10.1016/j.jgr.2018.02.004 [doi] PST - ppublish SO - J Ginseng Res. 2018 Oct;42(4):562-570. doi: 10.1016/j.jgr.2018.02.004. Epub 2018 Feb 16.