Quercetin inhibits human vascular smooth muscle cell proliferation and migration

Alcocer, Francisco; Whitley, David; Salazar-Gonzalez, Jesus F.; Jordan, William D.; Sellers, Marty T.; Eckhoff, Devin E.; Suzuki, Kaori; MacRae, Chastity; Bland, Kirby I.

doi:10.1067/msy.2002.119190

Cited by 48 publications

(29 citation statements)

References 28 publications

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“…In particular, quercetin shows specific inhibitory activity for cancer cell growth (Alcocer et al, 2002;Notoyart al., 2004;Ramos et al, 2008), but the mechanisms underlying the effects of quercetin in the induction of cell cycle arrest and apoptosis in human breast cancer cells are still unknown.…”

Section: Resultsmentioning

confidence: 99%

Antiproliferative effects of quercetin through cell cycle arrest and apoptosis in human breast cancer MDA-MB-453 cells

2008

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To explore the anticancer effects of the flavonoid quercetin on human breast cancer MDA-MB-453 cells via cell cycle regulation and the induction of apoptosis, the antiproliferative effect of quercetin was first examined by MTT assay. When MDA-MB-453 cells were treated with quercetin for various periods of time (3-24 hrs) and at various doses (1-100 microM), cell growth decreased significantly in a time-and dose-dependent manner. To elucidate the mechanism underlying the antiproliferative effect of quercetin, cell cycle progression and the induction of apoptosis in MDA-MB-453 cells exposed to 100 microM quercetin for 24 hrs were investigated. Quercetin caused a remarkable increase in the number of sub-G1 phase cells, and an Annexin-V assay revealed that exposure to quercetin affected apoptosis. Moreover, treatment with quercetin increased Bax expression but decreased Bcl-2 expression. Cleaved caspase-3 and PARP expression was also increased by quercetin. Thus, quercetin has probable anticancer activity. Our results suggest the existence of multiple pathways for the induction of cell cycle arrest and apoptosis by quercetin.

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Section: Resultsmentioning

confidence: 99%

Antiproliferative effects of quercetin through cell cycle arrest and apoptosis in human breast cancer MDA-MB-453 cells

2008

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“…1A). A significant reduction was observed with 25 M quercetin, whereas 50 -100 M quercetin (commonly used to study the effects of quercetin in vitro (31,32)) caused a dramatic almost 10-fold reduction in calcium accrual induced by warfarin (p Ͻ 0.05) and curbed calcium at levels characteristic of the noncalcifying cells. A similar potent inhibitory effect of 100 M quercetin on warfarin-induced calcium deposition was also observed in primary human VSMCs (Fig.…”

Section: Attenuation Of Warfarin-induced Vsmc Calcification Withmentioning

confidence: 99%

Quercetin Attenuates Warfarin-induced Vascular Calcification in Vitro Independently from Matrix Gla Protein

Beazley

Eghtesad

Nurminskaya

2013

Journal of Biological Chemistry

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Background: Molecular mechanism(s) of warfarin-induced vascular calcification are not well known. Results: Inhibition of ␤-catenin signaling with shRNA or quercetin prevents osteoblastic transformation and calcification in VSMCs and calcification in aortic rings treated with warfarin, independent from MGP and protein carboxylation. Conclusion: Quercetin inhibits vascular calcification via ␤-catenin signaling. Significance: Quercetin may be instrumental in treatment of warfarin-induced vascular calcification.

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“…Moreover, several cytostatic agents (eg, quercetin, mimosine, suramin, rapamycin, and troglitazone) reduced the migratory potential of VSMCs and tumor cells. [43][44][45][46][47][48] Likewise, 17␤-estradiol concurrently regulated cell growth and locomotion, leading to increased endothelial cell proliferation and migration and blockade of the chemotactic and mitogenic effects of PDGF-BB in VSMCs. 49 Inactivation of activator protein-1 and c-myc transcription factors also inhibited both proliferation and migration of cultured VSMCs, 50,51 and p53-deficient VSMCs displayed a higher rate of proliferation and migration than wild-type counterparts.…”

Section: Ink4amentioning

confidence: 99%

Coordinate Control of Proliferation and Migration by the p27 ^Kip1 /Cyclin-Dependent Kinase/Retinoblastoma Pathway in Vascular Smooth Muscle Cells and Fibroblasts

Dı́ez-Juan

Andrés

2003

Circulation Research

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Abstract-Previous studies have demonstrated a protective effect of the cyclin-dependent kinase (CDK) inhibitor p27 Kip1 against atherosclerosis and restenosis, two disorders characterized by abundant proliferation and migration of vascular smooth muscle cells and adventitial fibroblasts. These therapeutic effects might result from p27Kip1 -dependent suppression of both cell proliferation and migration. However, the interplay between cell growth and locomotion remains obscure. We show here that p27Kip1 inhibits cellular changes that normally occur during cell locomotion (eg, lamellipodia formation and reorganization of actin filaments and focal adhesions). Importantly, a p27Kip1 mutant lacking CDK inhibitory activity failed to inhibit vascular smooth muscle cell and fibroblast proliferation and migration. Moreover, a constitutively active mutant of the retinoblastoma protein (pRb) insensitive to CDK-dependent hyperphosphorylation inhibited both cell proliferation and migration. In contrast, inactivation of pRb by forced expression of the adenoviral oncogene E1A correlated with high proliferative and migratory activity. Collectively, these results suggest that cellular proliferation and migration are regulated in a coordinated manner by the p27 Kip1 Key Words: vascular smooth muscle cells Ⅲ fibroblasts Ⅲ cell cycle Ⅲ migration Ⅲ p27 Kip1 /pRb E xcessive proliferation and migration of vascular smooth muscle cells (VSMCs) and adventitial fibroblasts play an important role in the pathobiology of vascular occlusive disease (eg, atherosclerosis, in-stent restenosis, transplant vasculopathy, and vessel bypass graft failure). 1,2 Thus, understanding the molecular mechanisms that control hyperplastic growth and the locomotion of vascular cells should aid in the development of novel therapeutic strategies to reduce neointimal thickening.Cell cycle progression is controlled by several cyclindependent kinases (CDKs) that associate with regulatory cyclins. 3 Mitogenic stimuli activate CDK/cyclin holoenzymes, thus causing hyperphosphorylation of the retinoblastoma protein (pRb) and related "pocket" proteins from mid G 1 to mitosis. CDK-dependent pRb hyperphosphorylation releases E2F transcription factors, thus contributing to the expression of several growth and cell cycle-regulatory genes with functional E2F-binding sites in their promoters. 4 Interaction of CDKs/cyclins with CDK inhibitory proteins (CKIs) attenuates CDK activity and promotes growth arrest. 5 CKIs of the Cip/Kip family (p21 Cip1 , p27 Kip1 , and p57 Kip2 ) bind to and inhibit a wide spectrum of CDK/cyclin holoenzymes, whereas members of the Ink4 family (p16 Ink4a , p15 Ink4b , p18 Ink4c , and p19 Ink4d ) are specific for cyclin D-associated CDKs. Mitogenic and antimitogenic stimuli affect the rates of synthesis and degradation of CKIs as well as their redistribution among different CDK/cyclin pairs. 5 For example, p27Kip1 promotes the assembly of CDK4/cyclin D complexes, thus facilitating CDK2/cyclin E activation through the G 1 /S phase. Moreover, th...

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Quercetin inhibits human vascular smooth muscle cell proliferation and migration

Cited by 48 publications

References 28 publications

Antiproliferative effects of quercetin through cell cycle arrest and apoptosis in human breast cancer MDA-MB-453 cells

Antiproliferative effects of quercetin through cell cycle arrest and apoptosis in human breast cancer MDA-MB-453 cells

Quercetin Attenuates Warfarin-induced Vascular Calcification in Vitro Independently from Matrix Gla Protein

Coordinate Control of Proliferation and Migration by the p27 ^Kip1 /Cyclin-Dependent Kinase/Retinoblastoma Pathway in Vascular Smooth Muscle Cells and Fibroblasts

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Quercetin inhibits human vascular smooth muscle cell proliferation and migration

Cited by 48 publications

References 28 publications

Antiproliferative effects of quercetin through cell cycle arrest and apoptosis in human breast cancer MDA-MB-453 cells

Antiproliferative effects of quercetin through cell cycle arrest and apoptosis in human breast cancer MDA-MB-453 cells

Quercetin Attenuates Warfarin-induced Vascular Calcification in Vitro Independently from Matrix Gla Protein

Coordinate Control of Proliferation and Migration by the p27 Kip1 /Cyclin-Dependent Kinase/Retinoblastoma Pathway in Vascular Smooth Muscle Cells and Fibroblasts

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Coordinate Control of Proliferation and Migration by the p27 ^Kip1 /Cyclin-Dependent Kinase/Retinoblastoma Pathway in Vascular Smooth Muscle Cells and Fibroblasts