title: Kaurenic acid: Evaluation of the in vivo and in vitro antitumor activity on murine melanoma.
abstract: OBJECTIVE
  The in vivo and in vitro antitumor activity of kaurenic acid [kaur 16-en-19 oic acid] (KA) in melanoma was evaluated in a murine model in comparison with taxol (Tx).
  
  
  METHODS
  B16F1 melanoma was developed in C57BL/6 mice and cell cultures. Survival test, tumor growth, dissected-tumor measurements, histology, cytoxicity assay on cultured cells, and changes of apoptotic gene expression at mRNA level were analyzed.
  
  
  RESULTS
  KA showed antitumor effect in vivo and in vitro and compared with Tx, its antimelanoma activity was greater (P < 0.001). These results were confirmed by morphological analysis (P < 0.001). In melanoma cell cultures, KA IC(50) was 0.79 μM vs. 18.94 μM for Tx (P < 0.001). RT-PCR analysis demonstrated that Bcl-xL mRNA expression was altered in B16F1 mouse melanoma cells obtained from mice treated with either KA or Tx.
  
  
  CONCLUSIONS
  The data suggest that KA is active in animal melanoma models, both in vitro and in vivo, being its cytotoxic effects stronger than those exhibited by Tx. Further trials should be conducted to elucidate its mechanism of action in melanoma with respect to necrosis or apoptotic processes. Our results support other evidences indicating that KA is a potential chemotherapeutic agent against cancer that has to be widely explored.
authors.affiliation: Research Unit in Experimental Pharmacology, Department of Functional Sciences, School of Medicine, Universidad Centroccidental Lisandro Alvarado (UCLA), Barquisimeto, Venezuela.
authors.forename: Miriam C
authors.initials: MC
authors.lastname: Sosa-Sequera
authors.forename: Miguel
authors.initials: M
authors.lastname: Chiurillo
authors.forename: Jaime
authors.initials: J
authors.lastname: Moscoso
authors.forename: Josefina
authors.initials: J
authors.lastname: Dolinar
authors.forename: Omar
authors.initials: O
authors.lastname: Suarez
authors.forename: Natalia
authors.initials: N
authors.lastname: Neira
authors.forename: Hernan
authors.initials: H
authors.lastname: Mendoza
authors.forename: María
authors.initials: M
authors.lastname: Rivero-Paris