Esner Milan, Graifer Dmitry, Lleonart Matilde E, Lyakhovich Alex
Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Novosibirsk State University, Novosibirsk, Pirogova 2, 630090, Russia.
Cancer Lett. 2017 Jan 1;384:60-69. doi: 10.1016/j.canlet.2016.09.023. Epub 2016 Sep 28.
A significant part of current research studies utilizes various cellular models which imply specific antibiotics-containing media as well as antibiotics used for clonal selection or promoter de/activation. With the great success of developing such tools, mitochondria, once originated from bacteria, can be effectively targeted by antibiotics. For that reason, some studies propose antibiotics-targeting of mitochondria as part of anticancer therapy. Here, we have focused on the effects of various classes of antibiotics on mitochondria in cancer and non-cancer cells and demonlow mitochondrial membrane potential, reduced ATP production, altered morphology and lowered respiration rate which altogether suggested mitochondrial dysfunction (MDF). This was in parallel with increased level of reactive oxygen species (ROS) and decreased activity of mitochondrial respiration complexes. However, both survival and repopulation capacity of cancer cells was not significantly affected by the antibiotics, perhaps due to a glycolytic shift or activated autophagy. In turn, simultaneous inhibition of autophagy and treatment with antibiotics largely reduced tumorigenic properties of cancer cells suggesting potential strategy for anticancer therapy.
当前研究的很大一部分利用了各种细胞模型，这意味着使用特定的含抗生素培养基以及用于克隆选择或启动子激活/失活的抗生素。随着开发此类工具的巨大成功，曾经起源于细菌的线粒体可以被抗生素有效靶向。因此，一些研究提出将靶向线粒体的抗生素作为抗癌治疗的一部分。在这里，我们专注于各类抗生素对癌细胞和非癌细胞中线粒体的影响，并证明线粒体膜电位降低、ATP生成减少、形态改变和呼吸速率降低，这些都表明线粒体功能障碍（MDF）。这与活性氧（ROS）水平升高和线粒体呼吸复合物活性降低同时出现。然而，癌细胞的存活和再增殖能力并未受到抗生素的显著影响，这可能是由于糖酵解转变或自噬激活。反过来，同时抑制自噬和用抗生素治疗在很大程度上降低了癌细胞的致瘤特性，这表明了一种潜在的抗癌治疗策略。
