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线粒体靶向抗氧化剂MitoQ和MitoTEMPO不影响BRAF驱动的恶性黑色素瘤和KRAS驱动的小鼠肺癌进展。

Mitochondria-Targeted Antioxidants MitoQ and MitoTEMPO Do Not Influence BRAF-Driven Malignant Melanoma and KRAS-Driven Lung Cancer Progression in Mice.

作者信息

Le Gal Kristell, Wiel Clotilde, Ibrahim Mohamed X, Henricsson Marcus, Sayin Volkan I, Bergo Martin O

机构信息

Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences, University of Gothenburg, 405 30 Gothenburg, Sweden.

Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 405 30 Gothenburg, Sweden.

出版信息

Antioxidants (Basel). 2021 Jan 22;10(2):163. doi: 10.3390/antiox10020163.

Abstract

Cancer cells produce high levels of mitochondria-associated reactive oxygen species (ROS) that can damage macromolecules, but also promote cell signaling and proliferation. Therefore, mitochondria-targeted antioxidants have been suggested to be useful in anti-cancer therapy, but no studies have convincingly addressed this question. Here, we administered the mitochondria-targeted antioxidants MitoQ and MitoTEMPO to mice with BRAF-induced malignant melanoma and KRAS-induced lung cancer, and found that these compounds had no impact on the number of primary tumors and metastases; and did not influence mitochondrial and nuclear DNA damage levels. Moreover, MitoQ and MitoTEMPO did not influence proliferation of human melanoma and lung cancer cell lines. MitoQ and its control substance dTPP, but not MitoTEMPO, increased glycolytic rates and reduced respiration in melanoma cells; whereas only dTPP produced this effect in lung cancer cells. Our results do not support the use of mitochondria-targeted antioxidants for anti-cancer monotherapy, at least not in malignant melanoma and lung cancer.

摘要

癌细胞会产生高水平的线粒体相关活性氧(ROS),这些活性氧既能损伤大分子,也能促进细胞信号传导和增殖。因此,有人提出线粒体靶向抗氧化剂可能在抗癌治疗中有用,但尚无研究令人信服地解决这一问题。在此,我们给患有BRAF诱导的恶性黑色素瘤和KRAS诱导的肺癌的小鼠施用了线粒体靶向抗氧化剂MitoQ和MitoTEMPO,发现这些化合物对原发性肿瘤和转移灶的数量没有影响;也不影响线粒体和核DNA的损伤水平。此外,MitoQ和MitoTEMPO不影响人黑色素瘤和肺癌细胞系的增殖。MitoQ及其对照物质dTPP可提高黑色素瘤细胞的糖酵解速率并降低其呼吸作用,但MitoTEMPO无此作用;而只有dTPP在肺癌细胞中产生这种效果。我们的结果不支持将线粒体靶向抗氧化剂用于抗癌单一疗法,至少在恶性黑色素瘤和肺癌中不支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9fd/7912553/a6544d54c4f0/antioxidants-10-00163-g001.jpg

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