Regulation of mitochondrial dynamics in 2-methoxyestradiol-mediated osteosarcoma cell death.
Regulation of mitochondrial dynamics in 2-methoxyestradiol-mediated osteosarcoma cell death.
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DOI：
10.1038/s41598-020-80816-x
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发表时间：
2021-01-15
影响因子：
4.6
通讯作者：
Kmiec Z
中科院分区：
文献类型：
--
作者：
Gorska-Ponikowska M;Bastian P;Zauszkiewicz-Pawlak A;Ploska A;Zubrzycki A;Kuban-Jankowska A;Nussberger S;Kalinowski L;Kmiec Z
骨肉瘤是儿童和青少年最常见的恶性肿瘤之一。线粒体动力学（融合/裂变）和生物发生的研究在过去几年中受到了广泛关注，因为它们对癌细胞的死亡至关重要。具体而言，研究表明，细胞质动力蛋白相关蛋白1（Drp 1）的表达增加会触发线粒体分裂（分裂），从而激活BAX和下游内源性凋亡，有效抑制OS生长。在本研究中，将人OS细胞（转移性143 B OS细胞系）与2-甲氧基乙醇（2-ME）在生理学和药物相关浓度下孵育。通过MTT测定法测定细胞活力。共聚焦显微镜和蛋白质印迹法检测Drp 1和BAX蛋白水平的变化。线粒体分裂抑制剂1，MDIVI-1，在研究中使用，以进一步检查Drp 1在2-ME介导的作用机制中的作用。为了确定线粒体的定量和定性变化，使用电子显微镜。2-ME在所有使用浓度下增加OS细胞的线粒体分裂并诱导自噬。1 μM 2-ME使OS细胞线粒体面密度增加。随后，上调表达的Drp 1和BAX蛋白的2-ME强烈表明激活的内在凋亡途径。我们进一步观察了2-ME介导的OS细胞糖酵解状态的调节。因此，我们认为线粒体动力学的变化可能代表了2-ME抗癌作用的一种新机制。这一发现可能为提高化疗治疗OS的疗效开辟了新途径，但必须通过体内研究证实。
Osteosarcoma (OS) is one of the most malignant tumors of childhood and adolescence. Research on mitochondrial dynamics (fusion/fission) and biogenesis has received much attention in last few years, as they are crucial for death of cancer cells. Specifically, it was shown that increased expression of the cytoplasmic dynamin-related protein 1 (Drp1) triggers mitochondrial fission (division), which activates BAX and downstream intrinsic apoptosis, effectively inhibiting OS growth. In the presented study, human OS cells (metastatic 143B OS cell line) were incubated with 2-methoxyestradiol (2-ME) at both physiologically and pharmacologically relevant concentrations. Cell viability was determined by the MTT assay. Confocal microscopy and western blot methods were applied to examine changes in Drp1 and BAX protein levels. Mitochondrial Division Inhibitor 1, MDIVI-1, was used in the study to further examine the role of Drp1 in 2-ME-mediated mechanism of action. To determine quantitative and qualitative changes in mitochondria, electron microscopy was used. 2-ME at all used concentrations increased mitochondrial fission and induced autophagy in OS cells. At the concentration of 1 µM 2-ME increased the area density of mitochondria in OS cells. Subsequent, upregulated expression of Drp1 and BAX proteins by 2-ME strongly suggests the activation of the intrinsic apoptosis pathway. We further observed 2-ME-mediated regulation of glycolytic state of OS cells. Therefore, we suggest that changes of mitochondrial dynamics may represent a novel mechanism of anticancer action of 2-ME. This finding may open new approaches to improve the efficacy of chemotherapy in the treatment of OS, however, it has to be confirmed by in vivo studies.
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影响因子：
3
作者：
Kulke, Matthew H.;Chan, Jennifer A.;Meyerhardt, Jeffrey A.;Zhu, Andrew X.;Abrams, Thomas A.;Blaszkowsky, Lawrence S.;Regan, Eileen;Sidor, Carolyn;Fuchs, Charles S.
通讯作者：
Fuchs, Charles S.
影响因子：
3.7
作者：
Raharijaona M;Le Pennec S;Poirier J;Mirebeau-Prunier D;Rouxel C;Jacques C;Fontaine JF;Malthiery Y;Houlgatte R;Savagner F
通讯作者：
Savagner F
DOI：
10.3390/molecules190913267
发表时间：
2014-08-28
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Gorska M;Kuban-Jankowska A;Zmijewski MA;Gorzynik M;Szkatula M;Wozniak M
通讯作者：
Wozniak M
DOI：
10.1530/acta.0.1000154
发表时间：
1982-01-01
期刊：
ACTA ENDOCRINOLOGICA
影响因子：
--
作者：
BERG, D;THALER, F;KUSS, E
通讯作者：
KUSS, E
DNA链破裂是由神经元NOS的核劫持作为2-甲氧基丙二醇的抗癌作用。
影响因子：
--
作者：
Gorska M;Kuban-Jankowska A;Zmijewski M;Marino Gammazza A;Cappello F;Wnuk M;Gorzynik M;Rzeszutek I;Daca A;Lewinska A;Wozniak M
通讯作者：
Wozniak M