Disciplina de Biologia Celular, Departamento de Micro, Imuno e Parasitologia, Universidade Federal de São Paulo, Campus São Paulo, Brazil.
Biochem Biophys Res Commun. 2011 Jul 29;411(2):449-54. doi: 10.1016/j.bbrc.2011.06.176. Epub 2011 Jul 2.
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.
恶性黑色素瘤是最具侵袭性的癌症之一，近年来其发病率逐渐上升，占皮肤癌死亡人数的约 75%。这种不良预后是由于肿瘤对常规药物的耐药性，主要是通过细胞凋亡途径的失调。本工作的目的是研究α-蒎烯诱导的细胞死亡机制及其治疗应用。我们的结果表明，α-蒎烯能够诱导细胞凋亡，表现为线粒体膜电位早期破坏、活性氧产生增加、半胱天冬酶-3 活性增加、异染色质聚集、DNA 片段化和磷脂酰丝氨酸在细胞表面暴露。最重要的是，这种分子在治疗实验性转移性黑色素瘤方面非常有效，可减少肺肿瘤结节的数量。这是首次报道分离的α-蒎烯具有凋亡和抗转移活性。
