Achieving cholesterol goals with low-cost 3-hydroxy-3-methylglutaryl coenzyme-A (HMG Co-A) reductase inhibitors

Klein, Mary S.; Koffarnus, Robin L.; Minze, Molly G.; Ochoa, Pamella

doi:10.2146/sp150038

Cited by 2 publications

(1 citation statement)

References 10 publications

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“…The present study shows that simvastatin, a potent HMG-CoA reductase inhibitor, has the potential to dose-and time-dependently inhibit growth and induce apoptosis in osteosarcoma Statins, including simvastatin, inhibit HMG-CoA reductase via the mevalonate pathway, and are commonly used for cholesterol-lowering in cardiovascular disease (22,23). They exert numerous pleiotropic effects including modulation of inflammation, angiogenesis, neurodegeneration and cancer metastasis, as shown in vitro and in vivo (20).…”

Section: Discussionmentioning

confidence: 59%

Simvastatin exerts anticancer effects in osteosarcoma cell lines via geranylgeranylation and c-Jun activation

et al. 2018

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Osteosarcoma is the leading primary bone cancer in young adults and exhibits high chemoresistance rates. Therefore, characterization of both alternative treatment options and the underlying mechanisms is essential. Simvastatin, a cholesterol-lowering drug, has among its pleiotropic effects anticancer potential. Characterizing this potential and the underlying mechanisms in osteosarcoma is the subject of the present study. Human osteosarcoma cells (SaOS-2 and U2OS) were treated with simvastatin (4-66 µM) for 48 or 72 h. The effects of downstream substrate mevalonate (MA) or substrates for isoprenylation farnesyl pyrophosphate (FPP) and geranylgeranyl-pyrophosphate (GGPP) were evaluated using add-back experiments. Tumour growth using MTT assay, apoptosis, cell cycle and signalling cascades involved in simvastatin-induced manipulation were analysed. The results revealed that simvastatin dose-dependently inhibited cell growth. Simvastatin significantly induced apoptosis, increased the Bax/Bcl-2 ratio, and cleavage of caspase-3 and PARP protein. Simvastatin impaired cell cycle progression as shown by significantly increased percentages of cells in the G0/G1 phase and lower percentages of cells in the S phase. Gene expression levels of cell cycle-regulating genes (TP53, CDKN1A and CDK1) were markedly altered. These effects were not completely abolished by FPP, but were reversed by MA and GGPP. JNK and c-Jun phosphorylation was enhanced after simvastatin treatment, while those were abolished when either MA or GGPP were added. In conclusion, simvastatin acts primarily by reducing prenylation to induce apoptosis and reduce osteosarcoma cell growth. Particularly enhanced activation of c-Jun seems to play a pivotal role in osteosarcoma cell death.

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Section: Discussionmentioning

confidence: 59%

Simvastatin exerts anticancer effects in osteosarcoma cell lines via geranylgeranylation and c-Jun activation

et al. 2018

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Lactobacillus reuteri NCIMB 30242 (LRC) Inhibits Cholesterol Synthesis and Stimulates Cholesterol Excretion in Animal and Cell Models

Lee,

Park,

Kim

et al. 2023

Journal of Medicinal Food

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Achieving cholesterol goals with low-cost 3-hydroxy-3-methylglutaryl coenzyme-A (HMG Co-A) reductase inhibitors

Abstract: Due to the small sample size, statistical power was not met. Both race and dose were significant predictors of LDL reduction. When controlled for race, dose remained a significant predictor of LDL reduction. Further studies with low-cost statins in a larger patient population are needed.

Cited by 2 publications

References 10 publications

Simvastatin exerts anticancer effects in osteosarcoma cell lines via geranylgeranylation and c-Jun activation

Simvastatin exerts anticancer effects in osteosarcoma cell lines via geranylgeranylation and c-Jun activation

Lactobacillus reuteri NCIMB 30242 (LRC) Inhibits Cholesterol Synthesis and Stimulates Cholesterol Excretion in Animal and Cell Models

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