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Lipid-lowering drugs and cancer: an updated perspective

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Abstract

Statins and non-statin medications used for the management of dyslipidemia have been shown to possess antitumor properties. Since the use of these drugs has steadily increased over the past decades, more knowledge is required about their relationship with cancer. Lipid-lowering agents are heterogeneous compounds; therefore, it remains to be revealed whether anticancer potential is a class effect or related to them all. Here, we reviewed the literature on the influence of lipid-lowering medications on various types of cancer during development or metastasis. We also elaborated on the underlying mechanisms associated with the anticancer effects of antihyperlipidemic agents by linking the reported in vivo and in vitro studies.

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Data availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Abbreviations

3-MA:

3-Methyladenine

ACLY:

Adenosine triphosphate-citrate lyase

Akt:

Protein kinase B

ALA:

Alpha-linolenic acid

ANGPTLs:

Angiopoietin-like proteins

AMPK:

AMP-activated protein kinase

Baf-A1:

Bafilomycin A1

BCG:

Bacillus Calmette-Guérin

Bcl-2:

B-cell lymphoma-2

CDK:

Cyclin-dependent kinase

Cox-2:

Cyclooxygenase-2

DHA:

Docosahexaenoic acid

DMBA:

7,12 Dimethylbenzanthracene

DR5:

Death receptor 5

EGF:

Epidermal growth factor

ERK:

Extracellular signal-regulated kinase

EPA:

Eicosapentaenoic acid

FAK:

Focal adhesion kinase

FasL:

Fas Ligand

FGF2:

Fibroblast growth factor 2

FoxO:

Fork-head box O

FPP:

Farnesyl diphosphate

GGPP:

Geranylgeranyl diphosphate

GPR109A:

G-protein coupled receptor 109A

HER:

Human epidermal growth factor receptor

HDL:

High-density lipoprotein

HMG-CoA:

3-Hydroxyl-3 methylglutaryl coenzyme A

HOXA13:

Homeobox A13

HUVECs:

Human umbilical vein endothelial cells

IGF1:

Insulin-like growth factor 1

JAK:

Janus kinase

JNK:

C-Jun N-terminal kinase

LDL:

Low-density lipoprotein

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

MEG3:

Maternally expressed gene 3

mTOR:

Mammalian target of rapamycin

MMPs:

Matrix metallopeptidase

MTP:

Microsomal triglyceride transfer

NAD:

Nicotinamide adenine dinucleotide

NADP:

Nicotinamide adenine dinucleotide phosphate

NF-κB:

Nuclear factor κB

NSAIDs:

Nonsteroidal anti-inflammatory drugs

NNK:

Nicotine-derived nitrosamine ketone

NHANES:

National Health and Nutrition Examination Survey NPC1L1

NPC1L1:

Neimann-Pick C1-Like 1

ONECUT2:

One-cut homeobox-2

PCSK9:

Proprotein convertase subtilisin/kexin type 9

PI3K:

Phosphoinositide 3-kinases

PPARs:

Peroxisome proliferator-activated receptors

PTEN:

Phosphatase and tensin homolog

RAS:

Reticular activating system

Raf:

Rapidly accelerated fibrosarcoma

RCTs:

Randomized controlled trials

RIP:

Receptor-interacting serine/threonine

ROS:

Reactive oxygen species

SEAS:

Simvastatin and ezetimibe in Aortic Stenosis

SHARP:

Study of Heart and Renal Protection

SOCS3:

Suppressor of cytokine signaling 3

STAT:

Signal transducer and activator of transcription

SSTR5:

Somatostatin receptor subtype 5

TGF:

Transforming growth factor

TLR4:

Toll-like receptor 4

TNF:

Tumor necrosis factor

Traf1:

TNF receptor-associated factor 1

TRAIL:

Tumor necrosis factor-related apoptosis-inducing ligand

TSP-1:

Thombospndin-1

VEGF:

Vascular endothelial growth factor

VLDL:

Very low-density lipoprotein

WHO:

World Health Organization

ZDHHC5:

Zinc finger DHHC-type palmitoyltransferase 5

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Authors and Affiliations

  1. Cardio-Oncology Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

    Azin Alizadehasl

  2. Echocardiography Research CenterRajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

    Azin Alizadehasl, Maryam Sadat Alavi, Shabnam Boudagh, Somaye Mohebi, Leila Aliabadi, Mahsa Akbarian & Parisa Ahmadi

  3. Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran

    Mohaddeseh Sadat Alavi

  4. Department of Medicine and Surgery, University of Perugia, Perugia, Italy

    Massimo R. Mannarino

  5. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  6. Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

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  1. Azin Alizadehasl
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  2. Maryam Sadat Alavi
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  10. Amirhossein Sahebkar
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AS: conceptualization, writing—review and editing; MSA, SM, MSA, LA, MA, PA: writing—original draft; AA, MRM, SB: writing—review and editing.

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Correspondence to Amirhossein Sahebkar.

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Alizadehasl, A., Alavi, M.S., Boudagh, S. et al. Lipid-lowering drugs and cancer: an updated perspective. Pharmacol. Rep 76, 1–24 (2024). https://doi.org/10.1007/s43440-023-00553-6

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