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Lipid-Soluble Ginseng Extract Induces Apoptosis and G0/G1 Cell Cycle Arrest in NCI-H460 Human Lung Cancer Cells

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Abstract

This study was performed to elucidate the anticancer mechanism of a lipid-soluble ginseng extract (LSGE) by analyzing induction of apoptosis and arrest of cell cycle progression using the NCI-H460 human lung cancer cell line. Proliferation of NCI-H460 cells was potently inhibited by LSGE in a dose-dependent manner. The cell cycle arrest at the G0/G1 phase in NCI-H460 cells was induced by LSGE. The percentage of G0/G1 phase cells significantly increased, while that of S phase cells decreased after treatment with LSGE. The expression levels of cyclin-dependent kinase2 (CDK2), CDK4, CDK6, cyclin D3 and cyclin E related to G0/G1 cells progression were also altered by LSGE. In addition, LSGE-induced cell death occurred through apoptosis, which was accompanied by increasing the activity of caspases including caspase-8, caspase-9 and caspase-3. Consistent with enhancement of caspase activity, LSGE increased protein levels of cleaved caspase-3, caspase-8, caspase-9, and poly-ADP-ribose polymerase (PARP). These apoptotic effects of LSGE were inhibited by the pan-caspase inhibitor Z-VAD-fmk. These findings indicate that LSGE inhibits NCI-H460 human lung cancer cell growth by cell cycle arrest at the G0/G1 phase and induction of caspase-mediated apoptosis.

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Abbreviations

CDK:

cyclin-dependent kinase

FITC:

fluorescein isothiocyanate

LSGE:

lipid-soluble ginseng extract

PARP:

poly-ADP-ribose polymerase

XTT:

Sodium 3′-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis (4-methoxy-6-nitro) benzene sulfonic acid hydrate

References

  1. Helms S (2004) Cancer prevention and therapeutics: Panax ginseng. Altern Med Rev 9:259–274

    Google Scholar 

  2. Szeto YT, Wong JWM, Wong SCY, Pak SC, Benzie IFF (2011) DNA protective effect of ginseng and the antagonistic effect of Chinese turnip: a preliminary study. Plant Foods Hum Nutr doi:10.1007/s11130-011-0209-5

  3. Roh YS, Kim HB, Kang CW, Kim BS, Nah SY, Kim JH (2010) Neuroprotective effects of ginsenoside Rg3 against 24-OH-cholesterol induced cytotoxicity in cortical neuron. J Ginseng Res 34:246–253

    Article  CAS  Google Scholar 

  4. Kim YS, Kang KS, Kim SI (1990) Study on antitumor and immunomodulating activities of polysaccharide fractions from Panax ginseng: Comparison of effects of neutral and acidic polysaccharide fraction. Arch Pharm Res 13:330–337

    Article  Google Scholar 

  5. Park EK, Choo MK, Han MJ, Kim DH (2004) Ginsenoside Rh1 possesses antiallergic and anti-inflammatory activities. Int Arch Allergy Immunol 133:113–120

    Article  CAS  Google Scholar 

  6. Park SE, Park C, Kim SH, Hossain MA, Kim MY, Chung HY, Son WS, Kim GY, Choi YH, Kim ND (2009) Korean red ginseng extract induces apoptosis and decreases telomerase activity in human leukemia cells. J Ethnopharmacol 121:304–312

    Article  CAS  Google Scholar 

  7. Oh M, Choi YH, Choi S, Chung H, Kim K, Kim SI, Kim DK, Kim ND (1999) Anti-proliferating effects of ginsenoside Rh2 on MCF-7 human breast cancer cells. Int J Oncol 14:869–875

    CAS  Google Scholar 

  8. Yun TK (2003) Experimental and epidemiological evidence on non-organ specific cancer preventive effect of Korean ginseng and identification of active compounds. Mutat Res 523–524:63–74

    Google Scholar 

  9. Matsunaga H, Katano M, Yamamoto H, Fujito H, Mori M, Takata K (1990) Cytotoxic activity of polyacetylene compounds in Panax ginseng C. A. Meyer. Chem Pharm Bull 38:3480–3482

    CAS  Google Scholar 

  10. Lee SD, Yoo G, Chae HJ, In MJ, Oh NS, Hwang YK, Hwang WI, Kim DC (2009) Lipid-soluble extracts as the main source of anticancer activity in ginseng and ginseng marc. J Am Oil Chem Soc 86:1065–1071

    Article  CAS  Google Scholar 

  11. Kim JY, Lee KW, Kim SH, Wee JJ, Kim YS, Lee HJ (2002) Inhibitory effect of tumor cell proliferation and induction of G2/M cell cycle arrest by panaxytriol. Planta Med 68:119–122

    Article  CAS  Google Scholar 

  12. Park CE, Baek N, Park C (2001) Extraction of panaxynol and panaxydol compounds from Korean ginseng. Biotechnol Bioprocess Eng 6:433–437

    Article  CAS  Google Scholar 

  13. Lee SD, Park SK, Lee ES, Kim HM, Lee CW, Lee K, Lee KH, Kang MR, Lee KS, Lee J, Hwang WI, Kim DC (2010) A lipid-soluble red ginseng extract inhibits the growth of human lung tumor xenografts in nude mice. J Med Food 13:1–5

    Article  Google Scholar 

  14. Lee ES, Kim HM, Lee SD, Lee KS, Park SG, Lee CW, Lee K, Lee KH, Lee J, Hwang WI, In MJ, Kim DC (2010) A lipid-soluble ginseng extract inhibits human large cell lung cancer (NCI-H460) cells xenograft in vivo and the proliferation of cancer cells in vitro. J Korean Soc Appl Biol Chem 53:375–378

    Article  Google Scholar 

  15. Kim DC, Lee JY, In M, Chae HJ, Hwang YK, Hwang WI (2001) Effects of polyacetylenes in ginseng on activity of enzymes related to post-translational modification of ras protein and effects of petroleum ether extract of ginseng on progression of cell cycle. J Ginseng Res 25:156–161

    CAS  Google Scholar 

  16. Fisher D (1994) Apoptosis in cancer therapy: Crossing the threshold. Cell 78:539–542

    Article  CAS  Google Scholar 

  17. Hu H, Ahn NS, Yang X, Lee YS, Kang KS (2002) Ganoderma lucidum extract induces cell cycle arrest and apoptosis in MCF-7 human breast cancer cell. Int J Cancer 102:250–253

    Article  CAS  Google Scholar 

  18. Carney DN (2002) Lung cancer-time to move on from chemotherapy. N Engl J Med 346:126–128

    Article  Google Scholar 

  19. Voortman J, Checinska A, Giaccone G, Rodriguez JA, Kruyt FAE (2007) Bortezomib, but not cisplatin, induces mitochondria-dependent apoptosis accompanied by up-regulation of noxa in the non-small cell lung cancer cell line NCI-H460. Mol Cancer Ther 6:1046–1053

    Article  CAS  Google Scholar 

  20. Abdullah S, Abidin SAZ, Murd NA, Makpol S, Ngah WZW, Yusof YAM (2010) Ginger extract (Zingiber officinale) triggers apoptosis and G0/G1 cells arrest in HCT 116 and HT 29 colon cancer cell lines. Afr J Biochem 4:134–142

    Google Scholar 

  21. Wang CY, Lin KH, Yang CJ, Tsai JR, Hung JY, Wang PH, Hsu HK, Huang MS (2010) Toona sinensis extracts induced cell cycle arrest and apoptosis in the human lung large cell carcinoma. Kaohsiung J Med Sci 26:68–74

    Article  Google Scholar 

  22. Evrone E, Umbrichi CB, Korz D, Raman V, Loeb DM, Niranjan B, Marks J, Sukumar S (2001) Loss of cyclin D2 expression in the majority of breast cancer is associated with promoter hypermethylation. Cancer Res 61:2782–2787

    Google Scholar 

  23. Jeong HW, Lee HJ, Kho YH, Son KH, Han MY, Lim JS, Lee MY, Han DC, Ha JH, Kwon BM (2002) Biological effects of G1 phase arrest compound, sesquicillin, in human breast cancer cell lines. Bioorg Med Chem 10:3129–3134

    Article  CAS  Google Scholar 

  24. Pyo JS, Ju HK, Park JH, Kwon SW (2008) Determination of volatile biomarkers for apoptosis and necrosis by solid-phase microextractoion-gas chromatography/mass spectrometry: A pharmacometabolomic approach to cisplatin’s cytotoxicity to human lung cancer cell lines. J Chromatogr B 876:170–174

    Article  CAS  Google Scholar 

  25. Betz N, Farfan A, O’Brien M (2003) Detecting caspase activity in staurosporine-treated human neuroblastoma cells using fluorescent and luminescent methods. Cell Notes 7:9–11

    Google Scholar 

  26. Kim KS, Phee KH, Yoon JH, Lee JG, Lee JH, Yoo JB (2005) Gingko biloba extract (EGb 761) induces apoptosis by the activation of caspase-3 in oral cavity cancer cells. Oral Oncol 41:383–389

    Article  Google Scholar 

  27. Nicholson DW (2000) From bench to clinic with apoptosis-based therapeutic agents. Nature 407:810–816

    Article  CAS  Google Scholar 

  28. Yasmin AMY, Shahriza ZA, Looi ML, Shafina HMH, Harlianshah H, Noor AAH, Suzana M, Wan ZWN (2008) Ginger extract (Zingiber officinale Roscoe) triggers apoptosis in hepatocarcinogenesis induced rats. Med Health 3:263–274

    Google Scholar 

  29. Catalano MG, Fortunati N, Pugliese M, Costantino L, Poli R, Bosco O, Boccuzzi G (2005) Valproic acid induces apoptosis and cell cycle arrest in poorly differentiated thyroid cancer cells. J Clin Endocrinol Metab 90:1383–1389

    Article  CAS  Google Scholar 

  30. Cao P, Cai X, Lu W, Zhou F, Huo J (2011) Growth inhibition and induction of apoptosis in SHG-44 giloma cells by Chinese medicine formula “Pingliu Keli”. Evid Based Complement Alternat Med doi:10.1155/2011/958243

  31. Beevi SS, Mangamoori LN, Subathra M, Edula JR (2010) Hexane extract of Raphanus sativus L. roots inhibits cell proliferation and induces apoptosis in human cancer cells by modulating genes related to apoptotic pathway. Plant Foods Hum Nutr 65:200–209

    Article  Google Scholar 

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Acknowledgements

This study was supported in part by a grant (No. A101836) of the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea and a grant from the KRIBB Research Initiative Program.

Conflicts of Interest

There are no actual conflicts of interest.

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Authors and Affiliations

  1. Bio-evaluation center, Korea Research Institute of Bioscience and Biotechnology, Ochang, 363-883, Republic of Korea

    Moo Rim Kang, Hwan Mook Kim, Jong Soon Kang & Kiho Lee

  2. Department of Food and Nutrition, College of Health Science, Korea University, Seoul, 136-703, Republic of Korea

    Sung Dong Lee

  3. Department of Life Science, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, 120-750, Republic of Korea

    Dong-Hoon Hyun

  4. College of Pharmacy, Korea University, Chochiwon, 339-700, Republic of Korea

    Song-Kyu Park

  5. Department of Human Nutrition and Food Science, Chungwoon University, Hongseong, 350-701, Republic of Korea

    Man-Jin In & Dong Chung Kim

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  1. Moo Rim Kang
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Correspondence to Song-Kyu Park or Dong Chung Kim.

Additional information

Moo Rim Kang and Hwan Mook Kim contributed equally to this work.

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Kang, M.R., Kim, H.M., Kang, J.S. et al. Lipid-Soluble Ginseng Extract Induces Apoptosis and G0/G1 Cell Cycle Arrest in NCI-H460 Human Lung Cancer Cells. Plant Foods Hum Nutr 66, 101–106 (2011). https://doi.org/10.1007/s11130-011-0232-6

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  • DOI: https://doi.org/10.1007/s11130-011-0232-6

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