In vitro studies
Some of the most recent results from
in vitro studies on statin anticancer activity are presented in Table
Table1.1. 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.
Table 1
In vitro studies on the anticancer potential of statins
[TR]
[TD]
Cancer type
[/TD]
[TD]Cancer cell line[/TD]
[TD]Statin[/TD]
[TD]Observations[/TD]
[TD]Changes in intracellular signaling pathways[/TD]
[TD]Ref.[/TD]
[/TR]
[TR]
[TD]
Hepatoma
[/TD]
[TD]HepG2, Hep3B[/TD]
[TD]Simvastatin[/TD]
[TD]Inhibition of cell growth in a dose- and time-dependent manner; G0/G1 cell cycle arrest; Apoptosis[/TD]
[TD]AMPK activation and STAT3/Skp2 axis suppression, inducing p21 and p27 accumulation[/TD]
[TD][
21][/TD]
[/TR]
[TR]
[TD]
Ovarian cancer
[/TD]
[TD]Hey, SKOV3[/TD]
[TD]
Atorvastatin[/TD]
[TD]
Dose-dependent antiproliferative effect (1-250 µmol/L); Decrease in size and density of the cancer cells, and colony forming ability (at 150 µmol/L); G1-phase cell cycle arrest and S-phase decrease (at 150 µmol/L); Induction of apoptosis; Increased ROS levels in a dose-dependent manner; Induction of autophagy; Inhibition of cell adhesion and invasion[/TD]
[TD]Inhibition of Akt/mTOR and activation of MAPK pathway; Decreased Mcl-1 expression, variable effect on Bcl-2 expression, increased cleaved PARP protein expression; Increased expression of cellular stress protein (PERK and Bip) (at 150 µmol/L); Reduced expression of VEGF protein and MMP-9[/TD]
[TD][
22][/TD]
[/TR]
[TR]
[TD]
Breast cancer
[/TD]
[TD]SUM149, SUM159, MDA-MB-231[/TD]
[TD]Simvastatin[/TD]
[TD]Inhibition of proliferation, decrease in S-phase and increase in G1/S-phase arrest; Suppression of cell migration; Decrease in tumor sphere formation[/TD]
[TD]Down-regulation of phosphorylated FOXO3a in SUM149 and SUM159 cells; Variable effect on total FOXO3a expression[/TD]
[TD][
43][/TD]
[/TR]
[TR]
[TD]
Endometrial cancer
[/TD]
[TD]ECC-1, Ishikawa, primary cultures of endometrial cancer cells[/TD]
[TD]
Simvastatin[/TD]
[TD]
Dose-dependent antiproliferative effect in both cancer cell lines (0.01-50 µmol/L), and in 5/8 primary cultures; G0/G1-phase cell cycle arrest, decreased S-phase in ECC-1 cells; Decreased HMG-CoA reductase activity; Induction of apoptosis; Increased DNA damage, cellular oxidative stress; Reduced cell adhesion and invasion[/TD]
[TD]Inhibition of MAPK pathway, differential effects on the Akt/mTOR pathway; Increased cleaved caspase-3, decreased Bcl-2 expression, unmodified Mcl-1[/TD]
[TD][
20][/TD]
[/TR]
[TR]
[TD]
Osteosarcoma
[/TD]
[TD]MNNG/HOS[/TD]
[TD]Simvastatin[/TD]
[TD]Dose- and time-dependent antiproliferative effect (0.5-64 µmol/L); Dose-dependent morphological changes in treated cells: Cell shrinkage, loss of intercellular contact, reduced cell adherence, floating shapes; Dose-dependent suppression of cell migration, G0/G1-phase cell cycle arrest (16 µmol/L), and apoptosis[/TD]
[TD]Dose-dependent down-regulation of MMP-2 and MMP-9; Down-regulation of cyclin D1, CDK2 and CDK4, up-regulation of CDKIs, p21 Cip1 and p27 Kip1; Decrease in PI3K and phospho-Akt expression, while total AKt remained unmodified, up-regulation of Bax and cleaved PARP expression, decreased Bcl-2 expression[/TD]
[TD][
44][/TD]
[/TR]
[TR]
[TD]
Lung adenocarcinoma
[/TD]
[TD]A549, H1299, PC9, HCC827, H1975, H1435, PE8sc, CL1-0, Bm7, and immortalized normal lung epithelial cells (HBEC3KT)[/TD]
[TD]
Simvastatin[/TD]
[TD]
Higher cytotoxicity against LC cells with p53 mutation; Dose-dependent apoptosis; Reduced lipid rafts in mutant p53-bearing LC cells; Reduction in the migration distance; Promotes the nuclear transport of mutant p53 in Bm7 and H1435 cells[/TD]
[TD]Increased levels of cleaved PARP and cleaved caspase-3; No difference in the level of LC3-II; Decreased level of p53, and increased level of high molecular weight HSP-40[/TD]
[TD][
45][/TD]
[/TR]
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MAPK: Mitogen-activated protein kinase; ROS: Reactive oxygen species; HMG-CoA reductase: 3-hydroxy-3-methylglutaryl-coenzyme A reductase; AMPK: AMP-activated protein kinase; STAT3: Signal transducer and activator of transcription 3; skp2: S-phase kinase associated protein 2; Akt: Protein kinase B; mTOR: Mammalian target of rapamycin; PARP: Poly (ADP-ribose) polymerase; VEGF: Vascular endothelial growth factor; MMP: Matrix metalloproteinase; CDK: Cyclin-dependent kinase; CDKI: Cyclin-dependent kinase inhibitor; PI3K: Phosphoinositide 3-kinase; LC3: Microtubule-associated protein 1A/1B-light chain 3.