Effects of statins on the chemoresistance—The antagonistic drug-drug interactions versus the anti-cancer effects

Ahmadi, Yasin; Panahi, Yunes

doi:10.1016/j.biopha.2018.09.122

Cited by 29 publications

(21 citation statements)

References 138 publications

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“…Some of the most recent results from in vitro studies on statin anticancer activity are presented in Table 1 . By examining the results reported in the literature, several conclusions can be drawn, which are in agreement with findings previously reported by Osmak et al[ 11 ], Ahmadi et al[ 24 ], and others.…”

Section: Preclinical Studies Evaluating the Anticancer Effects Of Stasupporting

confidence: 90%

“…As a result, hydrophilic statins show an increased affinity for hepatic tissue, but not for other tissues. However, lipophilic statins achieve higher levels in extrahepatic tissues where they interfere with the synthesis of cholesterol[ 19 , 24 , 26 ]. Several in vitro studies on various cancer cell lines have reported lower anticancer efficacy for hydrophilic statins as opposed to lipophilic statins.…”

Section: Preclinical Studies Evaluating the Anticancer Effects Of Stamentioning

confidence: 99%

“…Several studies were conducted to evaluate the antitumor potential of lovastatin in combination with chemotherapy drugs such as cisplatin, 5-fluorouracil, daunorubicin, enzastaurin, and temozolomide, in various tumor cell lines. Lovastatin enhanced the cytotoxic effect of these drugs[ 24 , 37 ]. Enhanced antitumor effects were reported for simvastatin in combination with cisplatin, doxorubicin, gefitinib, vemurafenib/ selumetinib in nasopharyngeal carcinoma, bladder cancer, non-small cell LC, and melanoma, respectively[ 24 , 38 , 39 ].…”

Section: Preclinical Studies Evaluating the Anticancer Effects Of Stamentioning

confidence: 99%

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Statins in risk-reduction and treatment of cancer

Barbălată

Tefas

Achim

et al. 2020

WJCO

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Statins, which are competitive inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, reduce cholesterol blood levels and the risk of developing cardiovascular diseases and their related complications. In addition to this main activity, statins show pleiotropic effects such as antioxidant, anti-inflammatory and antiproliferative properties, with applications in many pathologies. Based on their antiproliferative properties, in vitro and in vivo studies have investigated their effects on various types of cancer ( i.e ., breast cancer, prostate cancer, colorectal cancer, ovarian cancer, lung cancer) with different genetic and molecular characteristics. Many positive results were obtained, but they were highly dependent on the physiochemical properties of the statins, their dose and treatment period. Combined therapies of statins and cytotoxic drugs have also been tested, and synergistic or additive effects were observed. Moreover, observational studies performed on patients who used statins for different pathologies, revealed that statins reduced the risk of developing various cancers, and improved the outcomes for cancer patients. Currently, there are many ongoing clinical trials aimed at exploring the potential of statins to lower the mortality and the disease-recurrence risk. All these results are the foundation of new treatment directions in cancer therapy.

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Section: Preclinical Studies Evaluating the Anticancer Effects Of Stasupporting

confidence: 90%

Section: Preclinical Studies Evaluating the Anticancer Effects Of Stamentioning

confidence: 99%

Section: Preclinical Studies Evaluating the Anticancer Effects Of Stamentioning

confidence: 99%

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Statins in risk-reduction and treatment of cancer

Barbălată

Tefas

Achim

et al. 2020

WJCO

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“…However, a clear connection between a determined statin and the capacity to interact and alter membrane bilayer properties cannot be fully established, mainly due to the different membrane models and experimental settings used. Clinical studies in cancer patients have suggested lower cancer mortality and less side effects with lipophilic statins compared to hydrophilic ones ( Ahern et al, 2011 ; Ahmadi et al, 2018 ; Beckwitt et al, 2018 ). In the last years the anti-tumor activity of statins was remarkably improved by using statins formulated in different drug delivery systems ( Coimbra et al, 2010 ; Alupei et al, 2015 ; Safwat et al, 2017a ; Matusewicz et al, 2019 ).…”

Section: Amphiphilic Molecules In Cancer Therapymentioning

confidence: 99%

New Insights Into Targeting Membrane Lipids for Cancer Therapy

Preta

2020

Front. Cell Dev. Biol.

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Modulation of membrane lipid composition and organization is currently developing as an effective therapeutic strategy against a wide range of diseases, including cancer. This field, known as membrane-lipid therapy, has risen from new discoveries on the complex organization of lipids and between lipids and proteins in the plasma membranes. Membrane microdomains present in the membrane of all eukaryotic cells, known as lipid rafts, have been recognized as an important concentrating platform for protein receptors involved in the regulation of intracellular signaling, apoptosis, redox balance and immune response. The difference in lipid composition between the cellular membranes of healthy cells and tumor cells allows for the development of novel therapies based on targeting membrane lipids in cancer cells to increase sensitivity to chemotherapeutic agents and consequently defeat multidrug resistance. In the current manuscript strategies based on influencing cholesterol/sphingolipids content will be presented together with innovative ones, more focused in changing biophysical properties of the membrane bilayer without affecting the composition of its constituents.

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“…Lastly, efforts to repurpose FDA approved drugs for cancer treatment have led to investigation of efficacy of combining statins with BH3 mimetics. Several preclinical studies have shown that statins can act as anticancer agents as well as synergize with chemotherapeutics by enhancing cytotoxicity or by increasing cellular concentration of chemotherapeutics [178]. Inhibition of a key enzyme in the cholesterol synthesis pathway—3-hydoxy-3-methylglutaryl coenzyme A reductase (HMGCR)—by simvastatin was found to synergize with venetoclax in inducing apoptosis in diffuse large B cell lymphoma and AML [179].…”

Section: Implications For Therapymentioning

confidence: 99%

Cancer Metabolism and the Evasion of Apoptotic Cell Death

Sharma

Boise

Shanmugam

2019

Cancers

111

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Cellular growth and proliferation depend upon the acquisition and synthesis of specific metabolites. These metabolites fuel the bioenergy, biosynthesis, and redox potential required for duplication of cellular biomass. Multicellular organisms maintain tissue homeostasis by balancing signals promoting proliferation and removal of cells via apoptosis. While apoptosis is in itself an energy dependent process activated by intrinsic and extrinsic signals, whether specific nutrient acquisition (elevated or suppressed) and their metabolism regulates apoptosis is less well investigated. Normal cellular metabolism is regulated by lineage specific intrinsic features and microenvironment driven extrinsic features. In the context of cancer, genetic abnormalities, unconventional microenvironments and/or therapy engage constitutive pro-survival signaling to re-program and rewire metabolism to maintain survival, growth, and proliferation. It thus becomes particularly relevant to understand whether altered nutrient acquisition and metabolism in cancer can also contribute to the evasion of apoptosis and consequently therapy resistance. Our review attempts to dissect a causal relationship between two cancer hallmarks, i.e., deregulated cellular energetics and the evasion of programmed cell death with primary focus on the intrinsic pathway of apoptosis.

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Effects of statins on the chemoresistance—The antagonistic drug-drug interactions versus the anti-cancer effects

Cited by 29 publications

References 138 publications

Statins in risk-reduction and treatment of cancer

Statins in risk-reduction and treatment of cancer

New Insights Into Targeting Membrane Lipids for Cancer Therapy

Cancer Metabolism and the Evasion of Apoptotic Cell Death

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