Simvastatin is effective in killing the radioresistant breast carcinoma cells

Aschenbrenner, Bertram; Negro, G.; Savic, Dragana; Sorokin, Maxim; Buzdin, Anton; Ganswindt, Ute; Čemažar, Maja; Serša, Gregor; Skvortsov, Sergej; Skvortsova, Ira

doi:10.2478/raon-2021-0020

Cited by 5 publications

(4 citation statements)

References 32 publications

(44 reference statements)

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“…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.…”

Section: Inducing Ferroptosis Enhances Radiosensitivitymentioning

confidence: 99%

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

Bian²,

Zheng³

et al. 2022

Front. Cell Dev. Biol.

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Ferroptosis is a kind of oxidative stress-dependent cell death characterized by iron accumulation and lipid peroxidation. It can work in conjunction with radiation to increase reactive oxygen species (ROS) generation and disrupt the antioxidant system, suppressing tumor progression. Radiation can induce ferroptosis by creating ROS, depleting glutathione, activating genes linked to DNA damage and increasing the expression of acyl-CoA synthetase long-chain family member 4 (ACSL4) in tumor cells. Furthermore, ferroptosis can enhance radiosensitivity by causing an iron overload, destruction of the antioxidant system, and lipid peroxidation. Radiation can also cause ferroptosis in normal cells, resulting in radiation injury. The role of ferroptosis in radiation-induced lung, intestinal, skin, and hematological injuries have been studied. In this review, we summarize the potential mechanisms linking ferroptosis, oxidative stress and radiation; analyze the function of ferroptosis in tumor suppression and radiation injury; and discuss the potential of ferroptosis regulation to improve radiotherapy efficacy and reduce adverse effects.

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Section: Inducing Ferroptosis Enhances Radiosensitivitymentioning

confidence: 99%

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

Bian²,

Zheng³

et al. 2022

Front. Cell Dev. Biol.

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“…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 ].…”

Section: Potential Treatment Strategies Through Targeting Lipophagymentioning

confidence: 99%

Emerging Roles of Lipophagy in Cancer Metastasis

Yin

Shan

Xia

et al. 2022

Cancers

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Obesity is a prominent risk factor for certain types of tumor progression. Adipocytes within tumor stroma contribute to reshaping tumor microenvironment (TME) and the metabolism and metastasis of tumors through the production of cytokines and adipokines. However, the crosstalk between adipocytes and tumor cells remains a major gap in this field. Known as a subtype of selective autophagy, lipophagy is thought to contribute to lipid metabolism by breaking down intracellular lipid droplets (LDs) and generating free fatty acids (FAs). The metastatic potential of cancer cells closely correlates with the lipid degradation mechanisms, which are required for energy generation, signal transduction, and biosynthesis of membranes. Here, we discuss the recent advance in the understanding of lipophagy with tumor lipid metabolism and review current studies on the roles of lipoghagy in the metastasis of certain human malignancies. Additionally, the novel candidate drugs targeting lipophagy are integrated for effective treatment strategies.

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“…Cholesterol biosynthesis has been reported to be involved in the radioresistance of breast cancer and pancreatic cancer. 7 , 8 Statins, the HMG-CoA inhibitors, have been used to treat breast cancer with increased recurrence free survival in preclinical and clinical studies. Previous studies showed that simvastatin could sensitize radioresistant breast cancer cell lines to radiation and reduced EMT transition and cellular migratory abilities.…”

mentioning

confidence: 99%

“…Previous studies showed that simvastatin could sensitize radioresistant breast cancer cell lines to radiation and reduced EMT transition and cellular migratory abilities. 8 However, further detailed mechanistic studies are needed to examine the roles statins played in cholesterol and lipid-metabolism for the radioresistance regulation in cancers.…”

mentioning

confidence: 99%