Pleiotropic effects of statins: A focus on cancer

Mazaher Ahmadi, Shayan Amiri, Stevan Pecic, Filip Machaj, Jakub Rosik, Marek J. Łos, Javad Alizadeh, Reza Mahdian, Simone C. da Silva Rosa, Dedmer Schaafsma, Shahla Shojaei, Tayyebeh Madrakian, Amir A. Zeki, Saeid Ghavami

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Article number165968
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1866
Issue number12
DOIs
StatePublished - Dec 1 2020

Keywords

  • Apoptosis
  • Autophagy
  • Cancer therapy
  • Chemotherapy
  • Mevalonate cascade
  • Prenylation

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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