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

被引:12
作者
Le Gal, Kristell [1 ,2 ]
Wiel, Clotilde [1 ,3 ]
Ibrahim, Mohamed X. [3 ]
Henricsson, Marcus [4 ]
Sayin, Volkan I. [1 ,2 ]
Bergo, Martin O. [3 ]
机构
[1] Univ Gothenburg, Sahlgrenska Ctr Canc Res, Dept Surg, Inst Clin Sci, S-40530 Gothenburg, Sweden
[2] Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, S-40530 Gothenburg, Sweden
[3] Karolinska Inst, Dept Biosci & Nutr, S-12343 Huddinge, Sweden
[4] Univ Gothenburg, Wallenberg Lab, Inst Med, S-40530 Gothenburg, Sweden
基金
英国医学研究理事会;
关键词
mitochondria-targeted antioxidants; melanoma; lung cancer; mouse models;
D O I
10.3390/antiox10020163
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1 / 13
页数:13
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