Planta Med 2004; 70(1): 12-16
DOI: 10.1055/s-2004-815448
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Rhein Inhibits the Growth and Induces the Apoptosis of Hep G2 Cells

Po-Lin Kuo1 , Ya-Ling Hsu1 , Lean Teik Ng2 , Chun-Ching Lin1
  • 1Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
  • 2Department of Food Science and Technology, Tajen Institute of Technology, Pingtung, Taiwan, ROC
Further Information

Publication History

Received: May 15, 2003

Accepted: November 8, 2003

Publication Date:
06 February 2004 (online)

Abstract

The effects of rhein on the human hepatoblastoma G2 (Hep G2) cell line were investigated in this study. The results showed that rhein not only inhibited Hep G2 cell growth but also induced apoptosis and blocked cell cycle progression in the G1 phase. An ELISA assay demonstrated that rhein significantly increased the expression of p53 and p21/WAF1 protein, which caused cell cycle arrest. An enhancement in CD95 and its two forms of ligands, membrane-bound CD95 ligand (mCD95L) and soluble CD95 ligand (sCD95L), might be responsible for the apoptotic effect induced by rhein. Taken together, p53 and the CD95/CD95L apoptotic system possibly participated in the antiproliferative activity of rhein in Hep G2 cells.

References

  • 1 Lin S, Li J J, Fujii M, Hou D X. Rhein inhibits TPA-induced activator protein-1 activation and cell transformation by blocking the JNK-dependent pathway.  Int J Oncol. 2003;  22 829-33
  • 2 Krumbiegel G, Schulz H U. Rhein and aloe-emodin kinetics from senna laxatives in man.  Pharmacology. 1993;  47 120-4
  • 3 Agarwal S K, Singh S S, Verma S, Kumar S. Antifungal activity of anthraquinone derivatives from Rheum emodin.  J Ethnopharmacol. 2000;  72 43-6
  • 4 Barnard D L, Huffman J H, Morris J L, Wood S G, Hughes B G, Sidwell R W. Evaluation of the antiviral activity of anthraquinones, anthrones and anthraquinone derivatives against human cytomegalovirus.  Antiviral Res. 1992;  17 63-77
  • 5 Castiglione S, Fanciulli M, Bruno T, Evangelista M, Del Carlo C, Paggi M G, Chersi A, Floridi A. Rhein inhibits glucose uptake in Ehrlich ascites tumor cells by alteration of membrane-associated functions.  Anticancer Drugs. 1993;  4 407-14
  • 6 Mendes A F, Caramona M M, de Carvalho A P, Lopes M C. Diacerhein and rhein prevent interleukin-1beta-induced nuclear factor-kappaB activation by inhibiting the degradation of inhibitor kappaB-alpha.  Pharmacol Toxicol. 2002;  91 22-8
  • 7 Pelletier J P, Mineau F, Boileau C, Martel-Pelletier J. Diacerein reduces the level of cartilage chondrocyte DNA fragmentation and death in experimental dog osteoarthritic cartilage at the same time that it inhibits caspase-3 and inducible nitric oxide synthase.  Clin Exp Rheumatol. 2003;  21 171-7
  • 8 Okuda K. Hepatocellular carcinogenesis: recent progress.  Hepatology. 1992;  15 948-63
  • 9 Sheu J C. Molecular mechanism of hepatocarcinogenesis.  J Gastroenterol Hepatol. 1997;  12 S309-13
  • 10 Wolfle D, Schmutte C, Westendorf J, Marquardt H. Hydroxyanthraquinones as tumor promoters: enhancement of malignant transformation of C3H mouse fibroblasts and growth stimulation of primary rat hepatocytes.  Cancer Res. 1990;  50 6540-4
  • 11 Muller M, Strand S, Hug H, Heinemann E M, Walczak H. Drug-induced apoptosis in hepatoma cells is mediated by the CD95 (APO-1/Fas) receptor/ligand system and involves activation of wild-type p53.  J Clin Invest. 1997;  99 403-13
  • 12 May P, May E. Twenty years of p53 research: structural and functional aspects of the p53 protein.  Oncogene. 1999;  18 7621-36
  • 13 Salgame P, Varadhachary A S, Primiano L L, Fincke J E, Muller S, Monestier M. An ELISA for detection of apoptosis.  Nucleic Acids Res. 1997;  25 680-1
  • 14 Jiang S, Song M J, Shin E C, Lee M O, Kim S J, Park J H. Apoptosis in human hepatoma cell lines by chemotherapeutic drugs via Fas-dependent and Fas-independent pathways.  Hepatology. 1999;  29 101-10
  • 15 Donehower L A, Harvey M, Slagle B L, McArthur M J, Montgomery CA J r, Butel J S. et al . Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours.  Nature. 1992;  356 215-21
  • 16 Brown J M, Wouters B G. Apoptosis, p53, and tumor cell sensitivity to anticancer agents.  Cancer Res. 1999;  59 1391-9
  • 17 Nagata S, Golstein P. The Fas death factor.  Science. 1995;  267 1449-56
  • 18 Lee S H, Shin M S, Lee H S, Bae J H, Lee H K, Kim H S. et al . Expression of Fas and Fas-related molecules in human hepatocellular carcinoma.  Hum Pathol. 2001;  32 250-6
  • 19 Kayagaki N, Kawasaki A, Ebata T, Ohmoto H, Ikeda S, Inoue S. et al . Metalloproteinase-mediated release of human Fas ligand.  J Exp Med. 1995;  182 1777-83
  • 20 Schneider P, Holler N, Bodmer J L, Hahne M, Frei K, Fontana A. et al . Conversion of membrane-bound Fas(CD95) ligand to its soluble form is associated with down regulation of its proapoptotic activity and loss of liver toxicity.  J Exp Med. 1998;  187 1205-13

Professor Chun-Ching Lin

Graduate Institute of Natural Products

College of Pharmacy

Kaohsiung Medical University

100 Shih-Chuan 1st Road

Kaohsiung 807

Taiwan

ROC

Phone: +886-7-3121101 ext. 2122

Fax: +886-7-3135215

Email: aalin@ms24.hinet.net

    >