Blanquer-Rosselló M Mar, Santandreu Francisca M, Oliver Jordi, Roca Pilar, Valle Adamo
Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Palma de Mallorca, Illes Balears, Spain.
Ciber Fisiopatología Obesidad y Nutrición (CB06/03), Instituto Salud Carlos III, Madrid, Spain.
J Cell Biochem. 2015 Sep;116(9):2039-48. doi: 10.1002/jcb.25158.
The adipokine leptin, known for its key role in the control of energy metabolism, has been shown to be involved in both normal and tumoral mammary growth. One of the hallmarks of cancer is an alteration of tumor metabolism since cancerous cells must rewire metabolism to satisfy the demands of growth and proliferation. Considering the sensibility of breast cancer cells to leptin, the objective of this study was to explore the effects of this adipokine on their metabolism. To this aim, we treated the MCF-7 breast cancer cell line with 50 ng/mL leptin and analyzed several features related to cellular and mitochondrial metabolism. As a result, leptin increased cell proliferation, shifted ATP production from glycolysis to mitochondria and decreased the levels of the glycolytic end-product lactate. We observed an improvement in ADP-dependent oxygen consumption and an amelioration of oxidative stress without changes in total mitochondrial mass or specific oxidative phosphorylation (OXPHOS) complexes. Furthermore, RT-PCR and western blot showed an up-regulation for genes and proteins related to biogenesis and mitochondrial dynamics. This expression signature, together with an increased mitophagy observed by confocal microscopy suggests that leptin may improve mitochondrial quality and function. Taken together, our results propose that leptin may improve bioenergetic efficiency by avoiding the production of reactive oxygen species (ROS) and conferring benefits for growth and survival of MCF-7 breast cancer cells.
脂肪因子瘦素以其在能量代谢控制中的关键作用而闻名，已被证明参与正常和肿瘤性乳腺生长。癌症的一个标志是肿瘤代谢的改变，因为癌细胞必须重新调整代谢以满足生长和增殖的需求。考虑到乳腺癌细胞对瘦素的敏感性，本研究的目的是探讨这种脂肪因子对其代谢的影响。为此，我们用50 ng/mL瘦素处理MCF-7乳腺癌细胞系，并分析了与细胞和线粒体代谢相关的几个特征。结果，瘦素增加了细胞增殖，将ATP产生从糖酵解转移到线粒体，并降低了糖酵解终产物乳酸的水平。我们观察到ADP依赖性氧消耗增加，氧化应激改善，而线粒体总质量或特定氧化磷酸化（OXPHOS）复合物没有变化。此外，RT-PCR和蛋白质印迹显示与生物发生和线粒体动力学相关的基因和蛋白质上调。这种表达特征，连同共聚焦显微镜观察到的线粒体自噬增加，表明瘦素可能改善线粒体质量和功能。综上所述，我们的结果表明，瘦素可能通过避免活性氧（ROS）的产生来提高生物能量效率，并为MCF-7乳腺癌细胞的生长和存活带来益处。
