Planta Med 2002; 68(11): 971-974
DOI: 10.1055/s-2002-35659
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Ginsenosides Inhibit EGF-Induced Proliferation of Renal Proximal Tubule Cells via Decrease of c-fos and c-jun Gene Expression in vitro

Ho Jae Han1 , Byeong Cheol Yoon1 , Sang Hern Lee2 , Soo Hyun Park1 , Ji Yeong Park1 , Young Joon Oh1 , Yun Jung Lee1
  • 1Department of Veterinary Physiology, College of Veterinary Medicine, Hormone Research Center, Chonnam National University, Kwangju 500-757, Korea
  • 2College of Veterinary Medicine & School of Agricultural Biotechnology, Seoul National University, Suwon, Korea
Further Information

Publication History

Received: March 8, 2002

Accepted: June 8, 2002

Publication Date:
26 November 2002 (online)

Abstract

Recent epidemiological studies have demonstrated that ginseng intake is associated with a reduced risk for environmentally related cancers. However, the effects of ginsenosides on the proliferation of renal proximal tubule cells have not yet elucidated. This study investigated the effect of total ginsenosides, protopanaxatriol (PT) saponin, and protopanaxadiol (PD) saponin fraction on epidermal growth factor (EGF)-induced renal cell proliferation and, furthermore, c-fos and c-jun gene expression. In the present study, total ginsenosides (10-6 g/ml) completely blocked EGF-induced DNA synthesis and cell growth. In contrast, the PT and PD fractions partially blocked it. In addition, the EGF-induced increase of c-fos and c-jun gene expression was completely blocked by total ginsenosides and partially by PT and PD saponins. In conclusion, ginsenosides, in part, inhibit EGF-induced cell proliferation via decrease of c-fos and c-jun gene expression in primary cultured rabbit renal proximal tubular cells (PTCs).

Abbreviations

EGF:epidermal growth factor

PD:protopanaxadiol

PT:protopanaxatriol

PTCs:primary cultured renal proximal tubule cells

References

  • 1 Kitts D, Hu C. Efficacy and safety of ginseng.  Public Health Nutrition.. 2000;  3 473-85
  • 2 Attele A S, Wu J A, Yuan C S. Ginseng pharmacology: multiple constituents and multiple actions.  Biochemical Pharmacology. 1999;  58 1685-93
  • 3 Yun T K. Experimental and epidemiological evidence of the cancer preventive effects of Panax ginseng C. A.  Meyer, Nutrional Review. 1996;  54 S71-81
  • 4 Xiaoguang C, Hongyan L, Xiahong L, Zhaodi F, Yan L, Lihua T, Rui R. Cancer chemopreventive and therapeutic activities of red ginseng.  Journal of Ethnopharmacology. 1998;  60 71-8
  • 5 Jacobsson B, Lignelid H, Bergerheim U S. Transthyretin and cystatin C are catabolized in proximal tubular epithelial cells and the proteins are not useful as markers for renal cell carcinomas.  Histopathology. 1995;  26 559-64
  • 6 Ramasubbu K, Gretz N, Bachmann S. Increased epithelial cell proliferation and abnormal extracellular matrix in rat polycystic kidney disease.  Journal of American Society Nephrology. 1998;  9 937-45
  • 7 Nowak G, Schnellmann R G. Integrative effects of EGF on metabolism and proliferation in renal proximal tubular cells.  American Journal of Physiology. 1995;  269 C1317-25
  • 8 Amato R J. Chemotherapy for renal cell carcinoma.  Seminar Oncology. 2000;  27 177-86
  • 9 Soldati F, Sticher O. HPLC separation and quantitative determination of ginsenosides from Panax ginseng, Panax quinquefolium and from ginseng drug preparations.  Planta Medica. 1980;  39 348-57
  • 10 Chung S D, Alavi N, Livingston D, Hiller S, Taub M. Characterization of primary rabbit kidney cultures that express proximal tubule functions in a hormonally defined medium.  Journal of Cellular Biology. 1982;  95 118-26
  • 11 Han H J, Park S H, Park K M, Yoon B C, Kim T S, Lee J H. Effect of caffeic acid on apical transporters’ dysfunction of renal proximal tubule cells under oxidative stress in vitro .  Planta Medica. 2002;  68 483-6
  • 12 Brett C M, Washington C B, Ott R J, Gutierrez M M, Giacomini K M. Interaction of nucleoside analogues with the sodium-nucleoside transport system in brush border membrane vesicles from human kidney.  Pharmacological Research. 1993;  10 423-6
  • 13 Liu Y, Wang L, Sha D, Zheng S, He J. Thin layer chromatographic studies on radix Ginseng, fructus Schisandrae and radix Salviae miltiorrhizae in yixinfumai granules.  Zhongguo Zhong Yao Za Zhi. 1992;  17 217-9
  • 14 Moch H, Sauter G, Buchholz N, Gasser T C, Bubendorf L, Waldman F M, Mihatsch M J. Epidermal growth factor receptor expression is associated with rapid tumor cell proliferation in renal cell carcinoma.  Human Pathology. 1997;  28 1255-9
  • 15 Liu W K, Xu S X, Che C T. Anti-proliferative effect of ginseng saponins on human prostate cancer cell line.  Life Science. 2000;  67(11) 1297-306
  • 16 Wakayabashi C, Hasegawa H, Murata J, Saiki I. In vivo antimetastatic action of ginseng protopanaxadiol saponins is based on their intestinal bacterial metabolites after oral administration.  Oncology Research. 1997;  9 411-7
  • 17 Shinkai K, Akedo H, Mukai M, Imamura F, Isoai A, Kobaysshi M, Kitagawa I. Inhibition of in vitro tumor cell invasion by ginsenoside Rg3.  Japanese Journal of Cancer Research.. 1996;  87 357-62
  • 18 Wakayabashi C, Murakami K, Hasegawa H, Murata J, Saiki I. An intestinal bacterial metabolites of ginseng protopanaxadiol saponins has the ability to induce apoptosis in tumor cells.  Biochemical Biophysical Research Communication. 1998;  246 725-30
  • 19 Kohler G, Veelken H, Rosenthal F, Mackensen A, Lindemann A, Schaefer H E, Lahn M. Oncogene and HSP-70 expression in primary tumor cell cultures of renal cell carcinoma compared to their corresponding cell line.  Anticancer Research. 1997;  17 3225-31
  • 20 Sato N, Kyakumoto S, Sawano K, Ota M. Proliferative signal transduction by epidermal growth factor (EGF) in the human salivary gland adenocarcinoma (HSG) cell line.  Biochemical Molecular Biology International. 1996;  38 597-606

Dr. Ho Jae Han

Department of Veterinary Physiology

College of Veterinary Medicine

Chonnam National University, Kwangju 500-757, Korea

Phone: 82-62-530-2831

Fax: 82-62-530-2809

Email: hjhan@chonnam.ac.kr

    >