S-adenosylmethionine increases the sensitivity of human colorectal cancer cells to 5-fluorouracil by inhibiting P-glycoprotein expression and NF-κB activation
| Autor: | Laura Mosca, Giulia Russo, Annapina Russo, Martina Pagano, Luigi Borzacchiello, Marina Porcelli, Giovanna Cacciapuoti, Luigi Mele |
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| Přispěvatelé: | Mosca, L., Pagano, M., Borzacchiello, L., Mele, L., Russo, A., Russo, G., Cacciapuoti, G., Porcelli, M. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
S-Adenosylmethionine
Colorectal cancer Cell Apoptosis Drug resistance Colorectal Neoplasm Multidrug resistance Tumor Cells Cultured Biology (General) Spectroscopy P-glycoprotein biology NF-kappa B Drug Synergism General Medicine Computer Science Applications Gene Expression Regulation Neoplastic Chemistry medicine.anatomical_structure Drug Therapy Combination Fluorouracil Colorectal Neoplasms Human Antimetabolites Antineoplastic QH301-705.5 5-Fluorouracil Article Catalysis Inorganic Chemistry Downregulation and upregulation medicine Humans ATP Binding Cassette Transporter Subfamily B Member 1 Physical and Theoretical Chemistry Combination therapy QD1-999 Molecular Biology Cell Proliferation business.industry Organic Chemistry Autophagy Cancer Apoptosi medicine.disease Drug Resistance Neoplasm Cancer cell Cancer research biology.protein business |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 9286, p 9286 (2021) International Journal of Molecular Sciences Volume 22 Issue 17 |
| Popis: | Colorectal cancer (CRC) is the second deadliest cancer worldwide despite significant advances in both diagnosis and therapy. The high incidence of CRC and its poor prognosis, partially attributed to multi-drug resistance and antiapoptotic activity of cancer cells, arouse strong interest in the identification and development of new treatments. S-Adenosylmethionine (AdoMet), a natural compound and a nutritional supplement, is well known for its antiproliferative and proapoptotic effects as well as for its potential in overcoming drug resistance in many kinds of human tumors. Here, we report that AdoMet enhanced the antitumor activity of 5-Fluorouracil (5-FU) in HCT 116p53+/+ and in LoVo CRC cells through the inhibition of autophagy, induced by 5-FU as a cell defense mechanism to escape the drug cytotoxicity. Multiple drug resistance is mainly due to the overexpression of drug efflux pumps, such as P-glycoprotein (P-gp). We demonstrate here that AdoMet was able to revert the 5-FU-induced upregulation of P-gp expression and to decrease levels of acetylated NF-κB, the activated form of NF-κB, the major antiapoptotic factor involved in P-gp-related chemoresistance. Overall, our data show that AdoMet, was able to overcome 5-FU chemoresistance in CRC cells by targeting multiple pathways such as autophagy, P-gp expression, and NF-κB signaling activation and provided important implications for the development of new adjuvant therapies to improve CRC treatment and patient outcomes. |
| Databáze: | OpenAIRE |
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