Danazol and clomiphene reduced the severity of hepatocarcinogenesis in the rat in vivo and cancer cells in vitro

N. A. Shamaan, W. Z. Wan Ngah, Z. Jarien, H. Abdullah Sani, Ibrahim Jantan, B. A K Khalid

Research output: Contribution to journalArticle

Abstract

The effects of danazol (5 mg/kg body weight/d) and chlomiphene (1.67 mg/kg body weight/d) on plasma γ-glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) activities, placental glutathione S-transferase (GSTP) and liver GGT activities immunohistochemically, during hepatocarcinogenesis in the rat were investigated. Hepatocarcinogenesis was induced by diethylnitrosamine (DEN) administration to the rat intraperitoneally, followed by feeding of 0.02% (w/w) 2-acetylaminofluorene (AAF) and partial hepatectomy. Danazol and clomiphene were dissolved in corn oil and administered daily to the rats intragastrically. The enzyme activities in the cancer-induced rats were significantly higher than the normal controls and the danazol and clomiphene treated rats. Formation of GGT- and GSTP-positive foci was evident in the cancer-induced rats and absent in the normal controls. Treatment of danazol and clomiphene significantly attenuated the enzyme activities and the formation of enzyme-positive foci in the cancer-induced rats. Both danazol and clomiphene were tested against HepG2 and Chang liver cells in culture. Cell proliferation was measured by the incorporation of 5-bromo-2'-deoxyuridine (BrdU) and viability was detected by the tetrazolium salt MTS. Clomiphene significantly reduced HepG2 cell viability and proliferation at doses greater than 10 ug/mL while danazol had no effect on both HepG2 and Chang liver cells in culture. The proliferation and viability of Chang liver cells were not affected by clomiphene at the doses used.

Original languageEnglish
Pages (from-to)67-72
Number of pages6
JournalAsia Pacific Journal of Pharmacology
Volume14
Issue number3
Publication statusPublished - 2000

Fingerprint

Danazol
Clomiphene
Neoplasms
Liver
Enzymes
Cell Culture Techniques
Body Weight
Cell Proliferation
Tetrazolium Salts
2-Acetylaminofluorene
Diethylnitrosamine
Corn Oil
gamma-Glutamyltransferase
Hep G2 Cells
Hepatectomy
Bromodeoxyuridine
In Vitro Techniques
Glutathione Transferase
Cell Survival

Keywords

  • Clomiphene
  • Danazol
  • Marker enzymes
  • Rat liver carcinogenesis

ASJC Scopus subject areas

  • Pharmacology

Cite this

Shamaan, N. A., Wan Ngah, W. Z., Jarien, Z., Abdullah Sani, H., Jantan, I., & Khalid, B. A. K. (2000). Danazol and clomiphene reduced the severity of hepatocarcinogenesis in the rat in vivo and cancer cells in vitro. Asia Pacific Journal of Pharmacology, 14(3), 67-72.

Danazol and clomiphene reduced the severity of hepatocarcinogenesis in the rat in vivo and cancer cells in vitro. / Shamaan, N. A.; Wan Ngah, W. Z.; Jarien, Z.; Abdullah Sani, H.; Jantan, Ibrahim; Khalid, B. A K.

In: Asia Pacific Journal of Pharmacology, Vol. 14, No. 3, 2000, p. 67-72.

Research output: Contribution to journalArticle

Shamaan, NA, Wan Ngah, WZ, Jarien, Z, Abdullah Sani, H, Jantan, I & Khalid, BAK 2000, 'Danazol and clomiphene reduced the severity of hepatocarcinogenesis in the rat in vivo and cancer cells in vitro', Asia Pacific Journal of Pharmacology, vol. 14, no. 3, pp. 67-72.
Shamaan, N. A. ; Wan Ngah, W. Z. ; Jarien, Z. ; Abdullah Sani, H. ; Jantan, Ibrahim ; Khalid, B. A K. / Danazol and clomiphene reduced the severity of hepatocarcinogenesis in the rat in vivo and cancer cells in vitro. In: Asia Pacific Journal of Pharmacology. 2000 ; Vol. 14, No. 3. pp. 67-72.
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