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Inhibitory effect of a biscoclaurine alkaloid, cepharanthin, on lung metastasis of Lewis lung carcinoma.

Abstract
The antimetastatic effect of cepharanthin with or without 5-fluorouracil (5-FU) was examined in an experimental model of lung metastasis induced by Lewis lung carcinoma (3LL) in C57BL/6crSlc mice. Injection of cepharanthin i.p. after removal of the implanted primary tumor inhibited the development of lung metastases. Combination therapy with cepharanthin plus 5-FU inhibited significantly the lung metastases. Lung metastases were inhibited by i.v. injection of peritoneal macrophages activated with cepharanthin. Cepharanthin depressed aniline hydroxylase and aminopyrine demethylase activities of the hepatic microsomal drug-metabolizing system in tumor-bearing mice. Moreover, the concentration of 5-FU in the tissues (lung, liver, kidney, spleen and blood) was increased significantly by coadministration of cepharanthin. A possible mechanism of the inhibition of lung metastases by treatment with cepharanthin may be that this drug acts through macrophage activation and depression of the hepatic microsomal drug-metabolizing system. These findings raise the possibility that combination therapy with cepharanthin plus 5-FU may have clinical value in the prevention of cancer metastasis.
AuthorsH Ito, H Ito, H Amano, H Noda
JournalJapanese journal of pharmacology (Jpn J Pharmacol) Vol. 56 Issue 2 Pg. 195-202 (Jun 1991) ISSN: 0021-5198 [Print] Japan
PMID1880998 (Publication Type: Journal Article)
Chemical References
  • Alkaloids
  • Benzylisoquinolines
  • cepharanthine
  • Aniline Hydroxylase
  • Aminopyrine N-Demethylase
  • Fluorouracil
Topics
  • Alkaloids (administration & dosage, pharmacology, therapeutic use)
  • Aminopyrine N-Demethylase (metabolism)
  • Aniline Hydroxylase (metabolism)
  • Animals
  • Benzylisoquinolines
  • Drug Therapy, Combination
  • Female
  • Fluorouracil (administration & dosage, pharmacology, therapeutic use)
  • Lung Neoplasms (prevention & control, secondary)
  • Macrophage Activation
  • Mice
  • Mice, Inbred C57BL
  • Microsomes, Liver (enzymology)
  • Neoplasm Transplantation
  • Peritoneal Cavity (cytology)

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