Selective cytotoxicity of betulinic acid on tumor cell lines, but not on normal cells.
Betulinic acid is a triterpene with selective cytotoxicity against melanoma, neuroectodermal and malignant brain tumor cell lines. In this study the betulinic acid activity was evaluated, in comparison with doxorubicin, on different human neoplastic and non-neoplastic cell lines and on proliferating normal lymphocytes. Growth inhibition was evident in all the neoplastic cell lines independently on p53 status and histotype. Antiproliferative activity of betulinic acid was related to a cytotoxic effect on two p53 wild-type and on one p53 mutant cell lines and to a cytostatic effect on one p53 mutant melanoma clone. At the same concentrations, normal cells were unaffected indicating a selective effect of this agent. A cytotoxic activity of doxorubicin was evident on all the tested systems. In vivo experiments, performed on one of these cell lines, confirmed the antineoplastic activity of this drug. These data support further preclinical studies of betulinic acid not confined to melanoma and neuroectodermal tumors independently of p53 status.
Zuco
Valentina
V
Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133, Milan, Italy.
Supino
Rosanna
R
Righetti
Sabina C
SC
Cleris
Loredana
L
Marchesi
Edoardo
E
Gambacorti-Passerini
Carlo
C
Formelli
Franca
F
D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005091:Exons; D016158:Genes, p53; D006801:Humans; D007700:Kinetics; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000633:toxicity*; D012016:Reference Values; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D000094062:Betulinic Acid
D000970:Antineoplastic Agents; D009828:Oleanolic Acid; D016159:Tumor Suppressor Protein p53; C118308:betulonic acid; D000094062:Betulinic Acid