ArticleBritish journal of pharmacology2002
Extracellular zinc stimulates ERK-dependent activation of p21(Cip/WAF1) and inhibits proliferation of colorectal cancer cells.
Article in British journal of pharmacology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed, 59 citations in OpenAlex.
- Zinc, copper, copper-to-zinc ratio, and other biometals in blood serum and tumor tissue of patients with colorectal cancer.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Article
- The Role of Micronutrients in Human Papillomavirus Infection, Cervical Dysplasia, and Neoplasm.Healthcare (Basel, Switzerland) · 2023Review
- Lovastatin reduces PEL cell survival by phosphorylating ERK1/2 that blocks the autophagic flux and engages a cross-talk with p53 to activate p21.IUBMB life · 2021Article
- Article
- Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases.Frontiers in pharmacology · 2018Review
- PNAS-4, an Early DNA Damage Response Gene, Induces S Phase Arrest and Apoptosis by Activating Checkpoint Kinases in Lung Cancer Cells.The Journal of biological chemistry · 2015Article
- Anticolorectal cancer effects and pharmacokinetic application of 2, 2-Bis [4-(4-amino-3-hydroxyphenoxy) phenyl] adamantane.International journal of clinical and experimental medicine · 2015Article
- Bitter melon extract impairs prostate cancer cell-cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model.Cancer prevention research (Philadelphia, Pa.) · 2011Article
- TGF-beta receptor levels regulate the specificity of signaling pathway activation and biological effects of TGF-beta.Biochimica et biophysica acta · 2009Article
- Glycine- and proline-rich glycoprotein regulates the balance between cell proliferation and apoptosis for ACF formation in 1,2-dimethylhydrazine-treated A/J mice.Molecular and cellular biochemistry · 2009Article
- Valproic acid induces differentiation and inhibition of proliferation in neural progenitor cells via the beta-catenin-Ras-ERK-p21Cip/WAF1 pathway.BMC cell biology · 2008Article
- NO mobilizes intracellular Zn2+ via cGMP/PKG signaling pathway and prevents mitochondrial oxidant damage in cardiomyocytes.Cardiovascular research · 2007Article
- Signaling pathways mediating manganese-induced toxicity in human glioblastoma cells (u87).Neurochemical research · 2006Article
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zinc is an important trace element in the body and is involved in both the proliferation and growth arrest of many kinds of cells including colorectal epithelial cells. The aim of this study was to identify the molecular mechanism of the growth regulation of colorectal cancer cells by extracellular zinc. Zinc-stimulated activation of the mitogen-activated protein kinase (MAPK) cascade was measured by immunoblotting and Elk-1 dependent trans-reporter gene expression, and zinc-stimulated p21(Cip/WAF1) activation by immunoblotting, Northern blot analysis and immunochemistry. Cell proliferation was measured by thymidine and bromodeoxyuridine (BrdU) incorporation. By treating colorectal cancer cells with 100 microM ZnCl2, MAPKs were activated in two different phases, the initial weak activation occurred within 5 min and this was followed by a stronger and more prolonged activation. Zinc concomitantly activated Raf-1-MEK-MAPK kinases, and induced Elk-1 dependent trans-reporter gene expression. Prolonged activation of MAPKs by 100 microM of ZnCl2 resulted in the induction and nuclear localization of p21(Cip/WAF1) and was related to the inhibition of both thymidine and BrdU incorporations. These results not only suggest the presence of a mechanism for p21(Cip/WAF1) dependent negative regulation of colorectal cancer cell growth by zinc but also suggest potential usage of zinc to control the growth of colorectal cancer cells.
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