Resveratrol inhibits the mevalonate pathway and potentiates the antiproliferative effects of simvastatin in rat theca-interstitial cells

Wong, Donna H.; Villanueva, Jesus A.; Cress, Amanda B.; Sokalska, Anna; Ortega, Israel; Dulęba, Antoni J.

doi:10.1016/j.fertnstert.2011.08.010

Cited by 34 publications

(28 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The following food groups and food extracts have high AMPKactivating capacity: resveratrol (red grape skin extract) [114][115][116][117][118], nootkatone (grapefruit extract) [119], ajoene (garlic extract) [120], BDIM (cruciferous vegetable extract) [19,121], and many others [122]. Medicines activate AMPK including Asa [16], Met [35], phenformin [123,124], rosiglitazone, and phenobarbital [125,126], and there may be others.…”

Section: Discussionmentioning

confidence: 99%

Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos

Bolnick

Abdulhasan

Kilburn

et al. 2016

J Assist Reprod Genet

View full text Add to dashboard Cite

Purpose The purpose of the present study is to test whether metformin, aspirin, or diet supplement (DS) BioResponse-3, 3′-Diindolylmethane (BR-DIM) can induce AMP-activated protein kinase (AMPK)-dependent potency loss in cultured embryos and whether metformin (Met) + Aspirin (Asa) or BR-DIM causes an AMPK-dependent decrease in embryonic development. Methods The methods used were as follows: culture post-thaw mouse zygotes to the two-cell embryo stage and test effects after 1-h AMPK agonists' (e.g., Met, Asa, BR-DIM, control hyperosmotic stress) exposure on AMPK-dependent loss of Oct4 and/or Rex1 nuclear potency factors, confirm AMPK dependence by reversing potency loss in two-cell-stage embryos with AMPK inhibitor compound C (CC), test whether Met + Asa (i.e., co-added) or DS BR-DIM decreases development of two-cell to blastocyst stage in an AMPK-dependent (CCsensitive) manner, and evaluate the level of Rex1 and Oct4 nuclear fluorescence in two-cell-stage embryos and rate of two-cell-stage embryo development to blastocysts. Result(s) Met, Asa, BR-DIM, or hyperosmotic sorbitol stress induces rapid~50-85 % Rex1 and/or Oct4 protein loss in twocell embryos. This loss is~60-90 % reversible by co-culture with AMPK inhibitor CC. Embryo development from twocell to blastocyst stage is decreased in culture with either Met + Asa or BR-DIM, and this is either >90 or~60 % reversible with CC, respectively. Conclusion These experimental designs here showed that Met-, Asa-, BR-DIM-, or sorbitol stress-induced rapid potency loss in two-cell embryos is AMPK dependent as suggested by inhibition of Rex1 and/or Oct4 protein loss with an AMPK inhibitor. The DS BR-DIM or fertility drugs (e.g., Met + Asa)Capsule Drugs metformin and aspirin and diet supplement BR-DIM cause AMPK-dependent potency loss and decrease embryonic development from two-cell to blastocyst stage. Reprod Genet (2016) 33:1027-1039 DOI 10.1007 that are used to enhance maternal metabolism to support fertility can also chronically slow embryo growth and block development in an AMPK-dependent manner.

show abstract

Section: Discussionmentioning

confidence: 99%

Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos

Bolnick

Abdulhasan

Kilburn

et al. 2016

J Assist Reprod Genet

View full text Add to dashboard Cite

show abstract

“…153 Resveratrol exhibits antiproliferative activity against cancer cells, which has been well elucidated using in vitro studies. 153, 196, 197 Melanoma cells express APE1/Ref-1 at greater than basal levels. Cells treated with resveratrol exhibit reduced AP-1 and NF-κB DNA-binding activity.…”

Section: Importance Of Phytochemicals In Modulating the Functions Of mentioning

confidence: 99%

APE1/Ref-1 as an emerging therapeutic target for various human diseases: phytochemical modulation of its functions

et al. 2014

View full text Add to dashboard Cite

Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional enzyme involved in the base excision repair (BER) pathway, which repairs oxidative base damage caused by endogenous and exogenous agents. APE1 acts as a reductive activator of many transcription factors (TFs) and has also been named redox effector factor 1, Ref-1. For example, APE1 activates activator protein-1, nuclear factor kappa B, hypoxia-inducible factor 1α, paired box gene 8, signal transducer activator of transcription 3 and p53, which are involved in apoptosis, inflammation, angiogenesis and survival pathways. APE1/Ref-1 maintains cellular homeostasis (redox) via the activation of TFs that regulate various physiological processes and that crosstalk with redox balancing agents (for example, thioredoxin, catalase and superoxide dismutase) by controlling levels of reactive oxygen and nitrogen species. The efficiency of APE1/Ref-1's function(s) depends on pairwise interaction with participant protein(s), the functions regulated by APE1/Ref-1 include the BER pathway, TFs, energy metabolism, cytoskeletal elements and stress-dependent responses. Thus, APE1/Ref-1 acts as a ‘hub-protein' that controls pathways that are important for cell survival. In this review, we will discuss APE1/Ref-1's versatile nature in various human etiologies, including neurodegeneration, cancer, cardiovascular and other diseases that have been linked with alterations in the expression, subcellular localization and activities of APE/Ref-1. APE1/Ref-1 can be targeted for therapeutic intervention using natural plant products that modulate the expression and functions of APE1/Ref-1. In addition, studies focusing on translational applications based on APE1/Ref-1-mediated therapeutic interventions are discussed.

show abstract

“…We also found that in these cells simvastatin inhibits activity of HMGCR and reduces cholesterol synthesis in a concentration-dependent fashion [6]. The effect of simvastatin on reduction of growth of theca-interstitial cells is not reversed in the presence of the cell-and mitochondrion-permeable forms of cholesterol (22-hydroxycholesterol and 25-hydroxycholesterol) indicating that the inhibition of proliferation of theca-interstitial cells is not due to reduced availability of cholesterol [4,7].…”

Section: Introductionmentioning

confidence: 63%

“…Comparable differences of effectiveness of different statins on cell proliferation and apoptosis were observed in pulmonary artery smooth muscle cells whereby the rank order of potency was: simvastatin > atorvastatin > pravastatin [26]. While the lipophilicity is likely to play a major role in the determining the ability of statins to act on non-hepatic cells, other factors unique 6 to individual cell types are also likely to be highly relevant. For example, in a study on proliferation of human saphenous vein smooth muscle cells, inhibitory effects of atorvastatin were significantly greater than the effects of either simvastatin or lovastatin [27].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Effects of Different Statins on Growth and Steroidogenesis of Rat Ovarian Theca-Interstitial Cells1

Sokalska

Stanley

Villanueva

et al. 2014

Biology of Reproduction

Self Cite

View full text Add to dashboard Cite

Statins are competitive inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA reductase, the rate-limiting enzyme of the cellular production of cholesterol and other products of the mevalonate pathway. Statins exert hepatic and extrahepatic effects, modulating the function of various tissues and organs, including ovaries. Previously, we have demonstrated that simvastatin inhibited cellular proliferation and reduced androgen production by ovarian theca-interstitial cells. The above actions are of translational relevance to the most common endocrine disorder among women in reproductive age: polycystic ovary syndrome. However, different statins may have distinctly different profiles of effects on cholesterol and androgens. The present study was designed to compare the effects of several statins on growth and steroidogenesis of rat theca-interstitial cells. The cells were incubated in the absence (control) or in the presence of simvastatin, lovastatin, atorvastatin, or pravastatin. Assessment of effects of statins on cell growth was carried out by evaluation of DNA synthesis and by estimation of the number of viable cells. Effects on steroidogenesis were evaluated by quantification of steroid production and expression of mRNA for the key enzyme regulating androgen production: Cyp17a1. Among tested statins, simvastatin exerted the greatest inhibitory effects on all tested parameters. The rank order of the effects of the tested statins is as follows: simvastatin > lovastatin > atorvastatin ≥ pravastatin. While the lipophilicity is likely to play a major role in determining the ability of statins to act on nonhepatic cells, other factors unique to individual cell types are also likely to be relevant.

show abstract

Resveratrol inhibits the mevalonate pathway and potentiates the antiproliferative effects of simvastatin in rat theca-interstitial cells

Cited by 34 publications

References 50 publications

Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos

Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos

APE1/Ref-1 as an emerging therapeutic target for various human diseases: phytochemical modulation of its functions

Comparison of Effects of Different Statins on Growth and Steroidogenesis of Rat Ovarian Theca-Interstitial Cells1

Contact Info

Product

Resources

About