Phenolic diterpenes derived from Hyptis incana induce apoptosis and G(2)/M arrest of neuroblastoma cells.

BACKGROUND: Neuroblastoma is one of the most commonly encountered solid tumors in the pediatric age group, and the prognosis of patients with advanced neuroblastoma is very poor. In this study, the antitumor effects of five phenolic diterpenes derived from Hyptis incana (Lamiaceae), a Brazilian medicinal plant, were examined on neuroblastoma cells. MATERIALS AND METHODS: Cytotoxicity was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptotic nuclear shrinkage was monitored by Hoechst 33342 staining. The cell-cycle status was evaluated by flow cytometry and protein alterations were monitored by western blotting. Differentiated cells were photographed and counted in a randomized fashion. RESULTS: All of the examined compounds exhibited significant cytotoxicity towards the neuroblastoma cells. In particular, 7-ethoxyrosmanol had a high degree of efficacy. Nuclear condensation and degradation of procaspase-3 and -9 were observed after treatment of the cells with these compounds. Moreover, phenolic diterpenes induced cell-cycle arrest in the G(2)/M phase. Rosmanol and epirosmanol tended to induce differentiation. CONCLUSION: Phenolic diterpenes isolated from H. incana have multiple antitumor effects on neuroblastoma cells.