Sulforaphane inhibits PDGF-induced proliferation of rat aortic vascular smooth muscle cell by up-regulation of p53 leading to G1/S cell cycle arrest

Yoo, Su-Hyang; Lim, Yong; Kim, Seung-Jung; Yoo, Kyu-Dong; Yoo, Hwan‐Soo; Jiang, Hong; Lee, Mi-Yea; Yun, Young Won

doi:10.1016/j.vph.2013.06.003

Cited by 31 publications

(38 citation statements)

References 28 publications

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“…Recent studies have shown that SFN attenuates neointima formation after carotid artery injury in rats with normal metabolic milieu [5, 6, 26]. However, it remains unknown as to whether SFN exhibits vasoprotective effects in the setting of diet-induced obesity.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have shown that SFN suppresses neointima formation in rat models of carotid artery injury [5, 6, 26]. In these studies, the vasoprotective effects of SFN have been observed in rats fed a normal diet with no obvious metabolic abnormalities.…”

Section: Discussionmentioning

confidence: 99%

“…In parallel, CON diet-fed mice were also subdivided into two groups to receive SFN or vehicle treatment. To study the in vivo effects of SFN, previous studies have employed different methods including oral, intravenous, intraperitoneal, and subcutaneous delivery [5, 6, 24–26]. Of note, oral administration and intravenous injection of SFN at lower dosage (0.5 mg/Kg) showed comparable plasma levels of SFN between 6 hr and 24 hr [25].…”

Section: Methodsmentioning

confidence: 99%

“…In particular, it induces phase-2 antioxidant enzymes that mitigate cellular oxidative stress through activation of nuclear factor erythroid 2-related factor 2 (Nrf2) [22]. Recent studies demonstrate that SFN exhibits beneficial effects in the vessel wall by targeting mitogenic and pro-inflammatory signaling in VSMCs [5, 6, 23], beyond its role as an antioxidant. The objectives of the present study are to determine the effects of SFN on: i) neointima formation after femoral artery injury in high-fat high-sucrose (HFHS) diet-fed mice; ii) body weight, food intake, caloric intake, epididymal white adipose tissue (eWAT) weight, and systemic metabolic parameters including hyperleptinemia, HOMA-IR (an index of insulin resistance), dyslipidemia, and blood pressure; and iii) leptin-induced key proliferative signaling in VSMCs.…”

Section: Introductionmentioning

confidence: 99%

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Sulforaphane improves dysregulated metabolic profile and inhibits leptin-induced VSMC proliferation: Implications toward suppression of neointima formation after arterial injury in western diet-fed obese mice

Shawky

Pichavaram

Shehatou

et al. 2016

The Journal of Nutritional Biochemistry

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Sulforaphane (SFN), a dietary phase-2 enzyme inducer that mitigates cellular oxidative stress through nuclear factor erythroid 2-related factor 2 (Nrf2) activation, is known to exhibit beneficial effects in the vessel wall. For instance, it inhibits vascular smooth muscle cell (VSMC) proliferation, a major event in atherosclerosis and restenosis after angioplasty. In particular, SFN attenuates the mitogenic and pro-inflammatory actions of platelet-derived growth factor (PDGF) and tumor necrosis factor-α (TNFα), respectively, in VSMCs. Nevertheless, the vasoprotective role of SFN has not been examined in the setting of obesity characterized by hyperleptinemia and insulin resistance. Using the mouse model of western diet-induced obesity, the present study demonstrates for the first time that subcutaneous delivery of SFN (0.5 mg/Kg/day) for ~3 weeks significantly attenuates neointima formation in the injured femoral artery [↓ (decrease) neointima/media ratio by ~60%; n = 5–8]. This was associated with significant improvements in metabolic parameters, including ↓ weight gain by ~52%, ↓ plasma leptin by ~42%, ↓ plasma insulin by ~63%, insulin resistance [↓ homeostasis model assessment of insulin resistance (HOMA-IR) index by ~73%], glucose tolerance (↓ AUCGTT by ~24%), and plasma lipid profile (e.g., ↓ triglycerides). Under in vitro conditions, SFN significantly decreased leptin-induced VSMC proliferation by ~23% (n = 5) with associated diminutions in leptin-induced cyclin D1 expression and the phosphorylation of p70S6kinase and ribosomal S6 protein (n = 3–4). The present findings reveal that, in addition to improving systemic metabolic parameters, SFN inhibits leptin-induced VSMC proliferative signaling that may contribute in part to the suppression of injury-induced neointima formation in diet-induced obesity.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sulforaphane improves dysregulated metabolic profile and inhibits leptin-induced VSMC proliferation: Implications toward suppression of neointima formation after arterial injury in western diet-fed obese mice

Shawky

Pichavaram

Shehatou

et al. 2016

The Journal of Nutritional Biochemistry

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show abstract

“…28 The functional importance of p53 in mediating cell cycle arrest and growth inhibition in VSMCs has been well documented. [47][48][49] In contrast, there is little information on the role of CHK1 in VSMCs. Interestingly, a recent study indicates that phosphorylation of CHK1 does not have a significant role in radiation-induced DNA damage response in stem cell-derived smooth muscle cells.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Targeting of RNA Polymerase I With the Small-Molecule CX-5461 for Prevention of Arterial Injury–Induced Neointimal Hyperplasia

Pang

Zhang

et al. 2017

ATVB

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Objective-RNA polymerase I (Pol I)-dependent rRNA synthesis is a determinant factor in ribosome biogenesis and thus cell proliferation. The importance of dysregulated Pol I activity in cardiovascular disease, however, has not been recognized. Here, we tested the hypothesis that specific inhibition of Pol I might prevent arterial injury-induced neointimal hyperplasia. Approach and Results-CX-5461 is a novel selective Pol I inhibitor. Using this tool, we demonstrated that local inhibition of Pol I blocked balloon injury-induced neointima formation in rat carotid arteries in vivo. Neointimal development was associated with augmented rDNA transcriptional activity as evidenced by the increased phosphorylation of upstream binding factor-1. The beneficial effect of CX-5461 was mainly mediated by inducing G2/M cell cycle arrest of proliferating smooth muscle cells without obvious apoptosis. CX-5461 did not induce p53 stabilization but increased p53 phosphorylation and acetylation and activated the ataxia telangiectasia mutated/ataxia telangiectasia and Rad3-related (ATR) pathway. Inhibition of ATR, but not of ataxia telangiectasia mutated, abolished the cytostatic effect of CX-5461 and p53 phosphorylation. In addition, inhibition of p53 or knockdown of the p53 target GADD45 mimicked the effect of ATR inhibition. In vivo experiments showed that the levels of phospho-p53 and acetyl-p53, and activity of the ataxia telangiectasia mutated/ATR pathway were all augmented in CX-5461-treated vessels. Conclusions-Pol

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Use of dietary phytochemicals to target inflammation, fibrosis, proliferation, and angiogenesis in uterine tissues: Promising options for prevention and treatment of uterine fibroids?

Islam

Akhtar

Ciavattini

et al. 2014

Molecular Nutrition Food Res

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Uterine leiomyomas (fibroids, myomas) are the most common benign tumors of female reproductive tract. They are highly prevalent, with 70–80% of women burdened by the end of their reproductive years. Fibroids are a leading cause of pelvic pain, abnormal vaginal bleeding, pressure on the bladder, miscarriage, and infertility. They are the leading indication for hysterectomy, and costs exceed 6 billion dollars annually in the United States. Unfortunately, no long-term medical treatments are available. Dysregulation of inflammatory processes are thought to be involved in the initiation of leiomyoma and extracellular matrix deposition, cell proliferation, and angiogenesis are the key cellular events implicated in leiomyoma growth. In modern pharmaceutical industries, dietary phytochemicals are used as source of new potential drugs for many kinds of tumors. Dietary phytochemicals may exert therapeutic effects by interfering with key cellular events of the tumorigenesis process. At present, a negligible number of phytochemicals have been tested as therapeutic agents against fibroids. In this context, our aim was to introduce some of the potential dietary phytochemicals that have shown anti-inflammatory, antiproliferative, antifibrotic, and antiangiogenic activities in different biological systems. This review could be useful to stimulate the evaluation of these phytochemicals as possible therapies for uterine fibroids.

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Sulforaphane inhibits PDGF-induced proliferation of rat aortic vascular smooth muscle cell by up-regulation of p53 leading to G1/S cell cycle arrest

Cited by 31 publications

References 28 publications

Sulforaphane improves dysregulated metabolic profile and inhibits leptin-induced VSMC proliferation: Implications toward suppression of neointima formation after arterial injury in western diet-fed obese mice

Sulforaphane improves dysregulated metabolic profile and inhibits leptin-induced VSMC proliferation: Implications toward suppression of neointima formation after arterial injury in western diet-fed obese mice

Therapeutic Targeting of RNA Polymerase I With the Small-Molecule CX-5461 for Prevention of Arterial Injury–Induced Neointimal Hyperplasia

Use of dietary phytochemicals to target inflammation, fibrosis, proliferation, and angiogenesis in uterine tissues: Promising options for prevention and treatment of uterine fibroids?

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