Suppression of mitochondrial respiration with local anesthetic ropivacaine targets breast cancer cells

Journal of Thoracic Disease
Xiaodan GongLishen Wang

Abstract

Retrospective studies on cancer patients who have received local anesthesia show a favorable decrease in tumor metastasis and recurrence. However, the mechanisms underlying the benefits of local anesthesia on cancer recurrence are not well understood. In this study, we investigated the biological effects of ropivacaine on breast cancer cells and the mechanisms of its action with emphasis on mitochondrial respiration. Ropivacaine significantly inhibited growth, survival, and anchorage-independent colony formation in two human breast cancer cell lines. It also acted synergistically with a 5-FU in breast cancer cells. Mechanistically, ropivacaine was found to inhibit mitochondrial respiration by suppressing mitochondrial respiratory complex I and II activities, leading to energy depletion, and oxidative stress and damage. The inhibitory effects of ropivacaine in breast cancer cells were abolished in mitochondrial respiration-deficient ρ0 cells, indicating that mitochondrial respiration is essential for the mechanism of action of ropivacaine. Ropivacaine inhibited phosphorylation of Akt, mTOR, rS6, and EBP1 in breast cancer cells, suggesting the association between Akt/mTOR signaling pathway and mitochondrial functions in breast ca...Continue Reading

Citations

Jul 10, 2019·Pain Medicine : the Official Journal of the American Academy of Pain Medicine·Ravi K Grandhi, Barbara Perona
Aug 9, 2020·Local and Regional Anesthesia·Juan P CataMaria F Ramirez
Mar 9, 2019·Journal of Bioenergetics and Biomembranes·Jingwen YangWeijen Ting
Aug 9, 2020·Frontiers in Cell and Developmental Biology·Daipeng ZhouPeng Xu

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