title: α-Pinene isolated from Schinus terebinthifolius Raddi (Anacardiaceae) induces apoptosis and confers antimetastatic protection in a melanoma model.
abstract: Malignant melanoma is one the most aggressive types of cancer and its incidence has gradually increased in the last years, accounting for about 75% of skin cancer deaths. This poor prognosis results from the tumor resistance to conventional drugs mainly by deregulation of apoptotic pathways. The aim of this work was to investigate the cell death mechanism induced by α-pinene and its therapeutic application. Our results demonstrated that α-pinene was able to induce apoptosis evidenced by early disruption of the mitochondrial potential, production of reactive oxygen species, increase in caspase-3 activity, heterochromatin aggregation, DNA fragmentation and exposure of phosphatidyl serine on the cell surface. Most importantly, this molecule was very effective in the treatment of experimental metastatic melanoma reducing the number of lung tumor nodules. This is the first report on the apoptotic and antimetastatic activity of isolated α-pinene.
authors.affiliation: Disciplina de Biologia Celular, Departamento de Micro, Imuno e Parasitologia, Universidade Federal de São Paulo, Campus São Paulo, Brazil. alisson@gmail.com
authors.forename: Alisson L
authors.initials: AL
authors.lastname: Matsuo
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Figueiredo
authors.forename: Denise C
authors.initials: DC
authors.lastname: Arruda
authors.forename: Felipe V
authors.initials: FV
authors.lastname: Pereira
authors.forename: Jorge A Borin
authors.initials: JA
authors.lastname: Scutti
authors.forename: Mariana H
authors.initials: MH
authors.lastname: Massaoka
authors.forename: Luiz R
authors.initials: LR
authors.lastname: Travassos
authors.forename: Patricia
authors.initials: P
authors.lastname: Sartorelli
authors.forename: João H G
authors.initials: JH
authors.lastname: Lago
mesh_terms: D027926:Anacardiaceae / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D000081008:Bicyclic Monoterpenes; D045744:Cell Line, Tumor; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008297:Male; D008546:Melanoma, Experimental / Q000517:prevention & control* / Q000556:secondary*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D039821:Monoterpenes / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D000081008:Bicyclic Monoterpenes; D039821:Monoterpenes; C005451:alpha-pinene