Folic acid inhibition of EGFR-mediated proliferation in human colon cancer cell lines
العنوان: | Folic acid inhibition of EGFR-mediated proliferation in human colon cancer cell lines |
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المؤلفون: | Fazlul H. Sarkar, Joseph L. Kinzie, Ahmed J. Khan, Richard Jaszewski, Abbas Zagnoon, Omer Kucuk, Ravi Dhar, Adhip P.N. Majumdar, Martin Tobi |
المصدر: | American Journal of Physiology-Cell Physiology. 277:C1142-C1148 |
بيانات النشر: | American Physiological Society, 1999. |
سنة النشر: | 1999 |
مصطلحات موضوعية: | medicine.medical_specialty, Physiology, Blotting, Western, Biology, medicine.disease_cause, Folic Acid, Cell surface receptor, Epidermal growth factor, Internal medicine, medicine, Anticarcinogenic Agents, Humans, Epidermal growth factor receptor, chemistry.chemical_classification, Cell growth, Cell Biology, Transforming Growth Factor alpha, Enzyme Activation, ErbB Receptors, Enzyme, Endocrinology, chemistry, Hematinics, Cancer research, biology.protein, Caco-2 Cells, Carcinogenesis, Tyrosine kinase, Cell Division, Transforming growth factor |
الوصف: | Although accumulating evidence suggests a chemopreventive role for folic acid in colon cancer, the regulation of this process in unknown. We hypothesize that supplemental folic acid exerts its chemopreventive role by inhibiting mucosal hyperproliferation, an event considered to be central to the initiation of carcinogenesis in the gastrointestinal tract. The present investigation examines the effect of supplemental folic acid on proliferation of Caco-2 and HCT-116 colon cancer cell lines. Furthermore, because certain tyrosine kinases, particularly epidermal growth factor receptor (EGFR), play a role in regulating cell proliferation, we also examined the folic acid-induced changes in tyrosine kinase activity and expression of EGFR. In Caco-2 and HCT-116 cells, maintained in RPMI 1640 medium containing 1 microg/ml folic acid, we observed that the supplemental folic acid inhibited proliferation in a dose-dependent manner. Pretreatment of HCT-116 and Caco-2 cell lines with supplemental folic acid (1.25 microg/ml) completely abrogated transforming growth factor-alpha (TGF-alpha)-induced proliferation in both cell lines. Tyrosine kinase activity and the relative concentration of EGFR were markedly diminished in both cell lines following a 24-h exposure to supplemental folic acid. The folic acid-induced inhibition of EGFR tyrosine kinase activity in colon cancer cell lines was also associated with a concomitant reduction in the relative concentration of the 14-kDa membrane-bound precursor form of TGF-alpha. In conclusion, our data suggest that supplemental folic acid is effective in reducing proliferation in two unrelated colon cancer cell lines and that EGFR tyrosine kinase appears to be involved in regulating this process. |
تدمد: | 1522-1563 0363-6143 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7bb4e0bfbb5a1d0ed62d263f7b2ae932 https://doi.org/10.1152/ajpcell.1999.277.6.c1142 |
رقم الأكسشن: | edsair.doi.dedup.....7bb4e0bfbb5a1d0ed62d263f7b2ae932 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15221563 03636143 |
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