Table 2.

Potential drugs for joint pharmacologic prevention of cardiovascular disease and cancer (Masoudkabir et al. [181])

Drug	Direct target	Indirect targets	Action on CVD	Action on cancer
Statins	HMG-CoAreductase inhibition	• AMPK activation • Inhibition of Cyclines & cycline-dependent kinases • Up-regulation of tumor-suppressors (p53, p27, p21) • Inhibition of PI3K, serineethreonine kinases, NF-κB, and MAPKs signaling pathways	Improving endothelial function Plaque stabilization ↓ Atherosclerosis progression ↓ Myocardial infarction and stroke ↓ Cardiovascular mortality	Tumor-suppressor and anti-cancer role through: ↑ Apoptosis ↓ Proliferation ↓ Invasion ↑ Radiosensitization ↓ DNA damage
ASA	Inhibition of COX1	• AMPK activation?	↓ Myocardial infarction and stroke ↓ Cardiovascular mortality	↓ Cancer incidence ↓ Cancer death
ACEIs/ARBs	ACE inhibition/angiotensin II receptor antagonism	• ↓ VEGF expression • PPAR-γ activation	Improving endothelial function Plaque stabilization ↓ Atherosclerosis progression ↓ Myocardial infarction and stroke ↓ Cardiovascular mortality	↓ Cancer incidence Tumor-suppressor and anti-cancer role through: ↓ DNA damage ↑ Apoptosis ↑ Differentiation ↓ Angiogenesis ↓ Cell growth
Metformin	Unknown	• AMPK activation		↓ Cancer incidence Tumor suppression by regulating cellular proliferation, cell cycle progression and cellular survival
TZDs	PPAR-γ agonism	• AMPK activation • Wnt/β-catenin signaling pathway inhibition • IGF-1 inhibition • Inhibition of leptin gene expression	↓ Coronary and carotid atherosclerosis ↓ Thrombus formation and acute myocardial infarction and stroke ↓ Blood pressure	Tumor suppression through: ↓ Angiogenesis ↑ Apoptosis ↓ Self-renewal of cancer cells ↑ Differentiation

HMG-CoA-reductase 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, AMPK Adenosine 50 monophosphate -activated protein kinase, PI3K phosphoinositide 3-kinase, NFekB nuclear factor kappa-B, MAPK mitogen-activated kinases, CVD cardiovascular disease, COX1 cyclooxygenase 1, ACEIs/ARBs angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists, ACE angiotensin-converting enzyme, VEGF vascular endothelial growth factor, PPAR-g peroxisome proliferator-activated receptor-g, TZDs thiazolidinediones