ArticleMolecular carcinogenesis2011
Grape seed extract upregulates p21 (Cip1) through redox-mediated activation of ERK1/2 and posttranscriptional regulation leading to cell cycle arrest in colon carcinoma HT29 cells.
Article in Molecular carcinogenesis, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Sustainable Grape Antioxidant Dietary Fiber Preserves Proximal Colonic Homeostasis via Hsp27 and AMPK Signaling.International journal of molecular sciences · 2025Article
- Grape seed proanthocyanidin extract induces apoptotic and autophagic cell death in rheumatoid arthritis fibroblast-like synoviocytes.Archives of rheumatology · 2022Article
- Phyto-polyphenols as potential inhibitors of breast cancer metastasis.Molecular medicine (Cambridge, Mass.) · 2018Review
- The comparative study among different fractions of muscadine grape 'Noble' pomace extracts regarding anti-oxidative activities, cell cycle arrest and apoptosis in breast cancer.Food & nutrition research · 2017Article
- Cristacarpin promotes ER stress-mediated ROS generation leading to premature senescence by activation of p21(waf-1).Age (Dordrecht, Netherlands) · 2016Article
- Protective Role of Grape Seed Proanthocyanidins Against Ccl4 Induced Acute Liver Injury in Mice.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
- Article
- Nutraceuticals as potential therapeutic agents for colon cancer: a review.Acta pharmaceutica Sinica. B · 2014Review
- Target identification of grape seed extract in colorectal cancer using drug affinity responsive target stability (DARTS) technique: role of endoplasmic reticulum stress response proteins.Current cancer drug targets · 2014Article
- Alteration of antioxidant enzymes and associated genes induced by grape seed extracts in the primary muscle cells of goats in vitro.PloS one · 2014Article
- Grape seeds: ripe for cancer chemoprevention.Cancer prevention research (Philadelphia, Pa.) · 2013Article
- Bitter melon juice activates cellular energy sensor AMP-activated protein kinase causing apoptotic death of human pancreatic carcinoma cells.Carcinogenesis · 2013Article
- Differential effects of grape seed extract against human colorectal cancer cell lines: the intricate role of death receptors and mitochondria.Cancer letters · 2013Article
- Identifying molecular targets of lifestyle modifications in colon cancer prevention.Frontiers in oncology · 2013Article
- Generation of reactive oxygen species by grape seed extract causes irreparable DNA damage leading to G2/M arrest and apoptosis selectively in head and neck squamous cell carcinoma cells.Carcinogenesis · 2012Article
- Tannic acid down-regulates the angiotensin type 1 receptor through a MAPK-dependent mechanism.Molecular endocrinology (Baltimore, Md.) · 2012Article
- Grape polyphenols inhibit Akt/mammalian target of rapamycin signaling and potentiate the effects of gefitinib in breast cancer.Nutrition and cancer · 2012Article
- Potential anticancer properties of grape antioxidants.Journal of oncology · 2012Article
- Homeostatic imbalance and colon cancer: the dynamic epigenetic interplay of inflammation, environmental toxins, and chemopreventive plant compounds.Frontiers in oncology · 2012Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Abnormalities in cell cycle progression provide unlimited replicative potential to cancer cells, and therefore targeting of key cell cycle regulators could be a sound cancer chemopreventive strategy. Earlier, we found that grape seed extract (GSE) increases Cip/p21 protein level and inhibits growth and induces apoptosis in human colon carcinoma HT29 cells both in vitro and in vivo. However, the mechanism of GSE-induced p21 upregulation and its role in biological efficacy of GSE are not known, which were investigated here. GSE treatment of HT29 cells resulted in a strong dose- and time-dependent phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2), consistent with p21 induction. The inhibition of sustained ERK1/2 activation by GSE using pharmacological inhibitors abrogated GSE-induced p21 upregulation. Furthermore, pretreatment of cells with N-acetylcysteine inhibited GSE-induced ERK1/2 phosphorylation as well as p21 upregulation, suggesting the involvement of GSE-induced oxidative stress as an upstream event. Consistent with this, GSE also decreased intracellular level of reduced glutathione. Next, we determined whether GSE-induced signaling regulates p21 expression at transcriptional and/or translational levels. GSE was found to increase the stability of p21 message with resultant increase in p21 protein level, but it did not alter the protein stability to a great extent. Importantly, knock-down of p21 abrogated GSE-induced G(1) arrest suggesting that p21 induction by GSE is essential for its G(1) arrest effect. Together, our results for the first time identify a central role of p21 induction and associated mechanism in GSE-induced cell cycle arrest in HT29 cells.
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