NecroX-5 prevents breast cancer metastasis by AKT inhibition via reducing intracellular calcium levels

Park,Jin-Hee; Kim,Hyoung Kyu; Jung,Hana; Kim,Ki Hyang; Kang,Mi Seon; Hong,Jun Hyuk; Yu,Byeng Chul; Park,Sungjae; Seo,Su-Kil; Choi,Il Whan; Kim,Soon Ha; Kim,Nari; Han,Jin; Park,Sae Gwang

doi:10.3892/ijo.2016.3789

NecroX-5 prevents breast cancer metastasis by AKT inhibition via reducing intracellular calcium levels

Authors:
- Jin-Hee Park
- Hyoung Kyu Kim
- Hana Jung
- Ki Hyang Kim
- Mi Seon Kang
- Jun Hyuk Hong
- Byeng Chul Yu
- Sungjae Park
- Su-Kil Seo
- Il Whan Choi
- Soon Ha Kim
- Nari Kim
- Jin Han
- Sae Gwang Park
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Affiliations: Department of Microbiology and Immunology, INJE University College of Medicine, Busan 614-735, Republic of Korea, Department of Physiology, INJE University College of Medicine, Busan 614-735, Republic of Korea, Department of Internal Medicine, INJE University College of Medicine, Busan 614-735, Republic of Korea, Department of Pathology, INJE University College of Medicine, Busan 614-735, Republic of Korea, Graduate School, Department of Preventive Medicine, Kosin University College of Medicine, Busan 602-702, Republic of Korea, LG Life Science, Ltd., R&D Park, Daejeon 305-380, Republic of Korea
Published online on: December 5, 2016 https://doi.org/10.3892/ijo.2016.3789
Pages: 185-192

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Abstract

A major goal of breast cancer research is to prevent the molecular events that lead to tumour metastasis. It is well-established that both cytoplasmic and mitochondrial reactive oxygen species (ROS) play important roles in cell migration and metastasis. Accordingly, this study examined the molecular mechanisms of the anti-metastatic effects of NecroX-5, a mitochondrial ROS scavenger. NecroX-5 inhibited lung cancer metastasis by ameliorating migration in a mouse model. In human cancer cells, the inhibition of migration by NecroX-5 is cell type-dependent. We observed that the effect of NecroX-5 correlated with a reduction in mitochondrial ROS, but mitochondrial ROS reduction by MitoQ did not inhibit cell migration. NecroX-5 decreased intracellular calcium concentration by blocking Ca2+ influx, which mediated the inhibition of cell migration, AKT downregulation and the reduction of mitochondrial ROS levels. However, the reduction of mitochondrial ROS was not associated with supressed migration and AKT downregulation. Our study demonstrates the potential of NecroX-5 as an inhibitor of breast cancer metastasis.

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