ArticleInvestigational new drugs2011
Tolfenamic acid decreases c-Met expression through Sp proteins degradation and inhibits lung cancer cells growth and tumor formation in orthotopic mice.
Article in Investigational new drugs, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 61 citations in OpenAlex.
- Sp1 Targeted PARP1 Inhibition Protects Cardiomyocytes From Myocardial Ischemia-Reperfusion Injury via Downregulation of Autophagy.Frontiers in cell and developmental biology · 2021Article
- Effect of Selected Nonsteroidal Anti-inflammatory Drugs on the Viability of Canine Osteosarcoma Cells of the D-17 Line:Journal of veterinary research · 2019Article
- Decursinol Angelate Inhibits LPS-Induced Macrophage Polarization through Modulation of the NFκB and MAPK Signaling Pathways.Molecules (Basel, Switzerland) · 2018Article
- Tolfenamic acid-induced alterations in genes and pathways in pancreatic cancer cells.Oncotarget · 2017Article
- Association of Sp1 and survivin in epithelial ovarian cancer: Sp1 inhibitor and cisplatin, a novel combination for inhibiting epithelial ovarian cancer cell proliferation.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Article
- Sp1-mediated transcriptional regulation of MALAT1 plays a critical role in tumor.Journal of cancer research and clinical oncology · 2015Article
- Validation of a UV Spectrometric Method for the Assay of Tolfenamic Acid in Organic Solvents.Journal of pharmaceutics · 2015Article
- Anti-tumor activity of non-steroidal anti-inflammatory drugs: cyclooxygenase-independent targets.Cancer letters · 2014Review
- The involvement of endoplasmic reticulum stress in the suppression of colorectal tumorigenesis by tolfenamic acid.Cancer prevention research (Philadelphia, Pa.) · 2013Article
- Anticancer activity of tolfenamic acid in medulloblastoma: a preclinical study.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Article
- Short-term treatment with tolfenamic acid improves cognitive functions in Alzheimer's disease mice.Neurobiology of aging · 2013Article
- Article
- Studies on tolfenamic acid-chitosan intermolecular interactions: effect of pH, polymer concentration and molecular weight.AAPS PharmSciTech · 2013Article
- Cross-talk between MET and EGFR in non-small cell lung cancer involves miR-27a and Sprouty2.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Development and characterization of novel polyurethane films impregnated with tolfenamic acid for therapeutic applications.BioMed research international · 2013Article
- Reconstruction of an integrated genome-scale co-expression network reveals key modules involved in lung adenocarcinoma.PloS one · 2013Article
- Unifying mechanisms of action of the anticancer activities of triterpenoids and synthetic analogs.Anti-cancer agents in medicinal chemistry · 2012Review
- MET genetic lesions in non-small-cell lung cancer: pharmacological and clinical implications.Translational lung cancer research · 2012Review
- Chemopreventive effects of tolfenamic acid against esophageal tumorigenesis in rats.Investigational new drugs · 2012Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nonsteroidal anti-inflammatory drug (NSAID), tolfenamic acid (TA) is emerging as a new anti-cancer agent. TA induces the degradation of specific Specificity protein (Sp) transcription factors, Sp1, Sp3 and Sp4 which are associated with tumor growth and metastasis. In this study we have evaluated the effect of TA on lung cancer using both in vitro and in vivo models. TA in a dose dependent manner inhibited proliferation and cell viability of two different lung cancer cells, A549 and CRL5803. TA treatment for 48 h significantly decreased the expression of Sp1, Sp3 and Sp4. The hepatocyte growth factor receptor, c-Met is overexpressed in a variety of cancers including lung cancer and Sp proteins mediate the regulation of c-Met. TA diminished the expression of c-Met protein and modulates its downstream signaling pathway. Furthermore, TA treatment significantly increased the number of apoptotic cells and pro-apoptotic markers c-PARP and Bax confirming the activation of apoptotic pathways. In vivo studies using the orthotopic mice model for lung cancer showed that TA (25 mg/kg/2 days and 50 mg/kg/2 days) resulted in a dose dependent decrease in tumor formation. The immunohistochemical staining of lung tissue showed high expression of Sp1, Sp3, Sp4, c-Met and phospho Met in control group and a dose dependent decrease in TA treated groups. The crucial findings of this study support that targeting c-Met with a potent inhibitor of Sp proteins is a robust strategy for the implications in lung cancer treatment and TA can serve as a therapeutic agent for this devastating disease.
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