Pleiotropic effects of statins: A focus on cancer

doi:10.1016/j.bbadis.2020.165968

Review

. 2020 Dec 1;1866(12):165968.

doi: 10.1016/j.bbadis.2020.165968. Epub 2020 Sep 12.

Pleiotropic effects of statins: A focus on cancer

Affiliations

¹ Department of Analytical Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran.
² Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, R4046 - 351 Taché Ave, Winnipeg, Manitoba R2H 2A6, Canada; Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada.
³ Department of Chemistry and Biochemistry, California State University Fullerton, CA, USA.
⁴ Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada; Department of Pathology, Pomeranian Medical University in Szczecin, Poland.
⁵ Biotechnology Center, Silesian University of Technology, Gliwice, Poland.
⁶ Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada; Biology of Breathing Theme, Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Canada.
⁷ Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
⁸ Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada.
⁹ Science Impact, Winnipeg, Canada.
¹⁰ College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
¹¹ University of California, Davis School of Medicine. Division of Pulmonary, Critical Care, and Sleep Medicine. U.C. Davis Lung Center, Davis, California, USA; Veterans Affairs Medical Center, Mather, California, USA.
¹² Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada; Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran; Research Institute of Oncology and Hematology, Cancer Care Manitoba, University of Manitoba, Winnipeg, Canada. Electronic address: saeid.ghavami@umanitoba.ca.

PMID: 32927022
DOI: 10.1016/j.bbadis.2020.165968

Free article

Review

Pleiotropic effects of statins: A focus on cancer

Mazaher Ahmadi et al. Biochim Biophys Acta Mol Basis Dis. 2020.

Free article

. 2020 Dec 1;1866(12):165968.

doi: 10.1016/j.bbadis.2020.165968. Epub 2020 Sep 12.

Authors

Affiliations

¹ Department of Analytical Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran.
² Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, R4046 - 351 Taché Ave, Winnipeg, Manitoba R2H 2A6, Canada; Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada.
³ Department of Chemistry and Biochemistry, California State University Fullerton, CA, USA.
⁴ Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada; Department of Pathology, Pomeranian Medical University in Szczecin, Poland.
⁵ Biotechnology Center, Silesian University of Technology, Gliwice, Poland.
⁶ Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada; Biology of Breathing Theme, Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Canada.
⁷ Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
⁸ Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada.
⁹ Science Impact, Winnipeg, Canada.
¹⁰ College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
¹¹ University of California, Davis School of Medicine. Division of Pulmonary, Critical Care, and Sleep Medicine. U.C. Davis Lung Center, Davis, California, USA; Veterans Affairs Medical Center, Mather, California, USA.
¹² Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada; Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran; Research Institute of Oncology and Hematology, Cancer Care Manitoba, University of Manitoba, Winnipeg, Canada. Electronic address: saeid.ghavami@umanitoba.ca.

PMID: 32927022
DOI: 10.1016/j.bbadis.2020.165968

Abstract

The statin drugs ('statins') potently inhibit hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase by competitively blocking the active site of the enzyme. Statins decrease de novo cholesterol biosynthesis and thereby reduce plasma cholesterol levels. Statins exhibit "pleiotropic" properties that are independent of their lipid-lowering effects. For example, preclinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types. Furthermore, statins show chemo-sensitizing effects by impairing Ras family GTPase signaling. However, whether statins have clinically meaningful anti-cancer effects remains an area of active investigation. Both preclinical and clinical studies on the potential mechanisms of action of statins in several cancers have been reviewed in the literature. Considering the contradictory data on their efficacy, we present an up-to-date summary of the pleiotropic effects of statins in cancer therapy and review their impact on different malignancies. We also discuss the synergistic anti-cancer effects of statins when combined with other more conventional anti-cancer drugs to highlight areas of potential therapeutic development.

Keywords: Apoptosis; Autophagy; Cancer therapy; Chemotherapy; Mevalonate cascade; Prenylation.

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Pleiotropic effects of statins: A focus on cancer

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Pleiotropic effects of statins: A focus on cancer

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