Simvastatin is effective in killing the radioresistant breast carcinoma cells

Abstract

Background Statins, small molecular 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are widely used to lower cholesterol levels in lipid-metabolism disorders. Recent preclinical and clinical studies have shown that statins exert beneficial effects in the management of breast cancer by increasing recurrence free survival. Unfortunately, the underlying mechanisms remain elusive. Materials and methods Simvastatin, one of the most widely prescribed lipophilic statins was utilized to investigate potential radiosensitizing effects and an impact on cell survival and migration in radioresistant breast cancer cell lines. Results Compared to parental cell counterparts, radioresistant MDA-MB-231-RR, T47D-RR andAu565-RR cells were characterized by upregulation of 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMGCR) expression accompanied by epithelial-to-mesenchymal transition (EMT) activation. Radioresistant breast cancer cells can be killed by simvastatin via mobilizing of a variety of pathways involved in apoptosis and autophagy. In the presence of simvastatin migratory abilities and vimentin expression is diminished while E-cadherin expression is increased. Conclusions The present study suggests that simvastatin may effectively eradicate radioresistant breast carcinoma cells and diminish their mesenchymal phenotypes.

Cooperation effects of radiation and ferroptosis on tumor suppression and radiation injury

“…It can inhibit GPX4 by regulating selenoprotein and CoQ biosynthesis through the MVA pathway ( Warner et al, 2000 ; Santoro, 2020 ). Statins have been confirmed to act as radiation sensitizers in various tumor cells ( Hutchinson and Marignol, 2017 ; Jin et al, 2018 ; Aschenbrenner et al, 2021 ). In general, the FSP1-CoQ (10)-NAD(P)H pathway is closely related to radiosensitivity, with CoQ being the most critical target.…”

Iron(III)-salophene catalyzes redox cycles that induce phospholipid peroxidation and deplete cancer cells of ferroptosis-protecting cofactors

“…Human triple-negative MDA-MB-231 breast cancer cells (passage number 46–85), human osteosarcoma U2OS (passage number 35–43) and MG63 cells (passage number 38–46), and human HepG2 heptocarcinoma cells (passage number 19–23) were cultured in DMEM (glucose 4.5 g/L) medium (Gibco, #11965092), human MCF7 breast cancer cells (passage number 6–18) were cultured in DMEM (glucose 4.5 g/L) with 1 mM sodium pyruvate (Gibco, #12539059) and 10 μg/mL human recombinant insulin (Sigma Aldrich, #I9278), and human A549 lung carcinoma cells (Sigma Aldrich, #86012804; passage number 13–17) were cultured in RPMI-1640 medium supplemented with l -glutamine (Merck, #R8758), and human T-47D luminal A breast cancer cells were cultured in RPMI-1640 medium supplemented with l -glutamine (Merck, #R8758) and 10 μg/mL bovine insulin. Radio-resistant T-47D cells (T-47D_RR) were generated from parental T-47D cells by repeated exposure to ionizing radiation (10 Gy) (16 MV x-ray) [ 54 ]. Invasive T-47D cells (T-47D_Invasive) were generated from parental T-47D cells by repeated selection of cells that efficiently migrate in Boyden chambers through uncoated 8 μm pore membranes towards 10 % fetal calf serum (FCS) as attractant [ 55 ].…”

Emerging Roles of Lipophagy in Cancer Metastasis

“…Taking metformin works in reducing adipocyte secretion of MCP-1 and prevents ovarian cancer metastasis by inhibiting MCP-1/CCR-2 axis [ 138 ]. By activating a variety of pathways involved in apoptosis and lipophagy, simvastatin can kill radioresistant breast cancer cells, as well as inhibit their migration abilities and vimentin expression [ 139 ]. An inhibitor of PFKFB3 called PFK-15 promotes lipophagy in gynecologic cancers and is also chemosensitive [ 140 ].…”