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Tytuł:
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S-Adenosylmethionine Increases the Sensitivity of Human Colorectal Cancer Cells to 5-Fluorouracil by Inhibiting P-Glycoprotein Expression and NF-κB Activation.
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Autorzy:
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Mosca L; Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', Via Luigi De Crecchio 7, 80138 Naples, Italy.
Pagano M; Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', Via Luigi De Crecchio 7, 80138 Naples, Italy.; Department of Pharmacy, University of Naples 'Federico II', Via Domenico Montesano 49, 80131 Naples, Italy.
Borzacchiello L; Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', Via Luigi De Crecchio 7, 80138 Naples, Italy.
Mele L; Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli', Via Luciano Armanni 5, 80138 Naples, Italy.
Russo A; Department of Pharmacy, University of Naples 'Federico II', Via Domenico Montesano 49, 80131 Naples, Italy.
Russo G; Department of Pharmacy, University of Naples 'Federico II', Via Domenico Montesano 49, 80131 Naples, Italy.
Cacciapuoti G; Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', Via Luigi De Crecchio 7, 80138 Naples, Italy.
Porcelli M; Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', Via Luigi De Crecchio 7, 80138 Naples, Italy.
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Źródło:
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International journal of molecular sciences [Int J Mol Sci] 2021 Aug 27; Vol. 22 (17). Date of Electronic Publication: 2021 Aug 27.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Original Publication: Basel, Switzerland : MDPI, [2000-
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MeSH Terms:
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Drug Resistance, Neoplasm*
ATP Binding Cassette Transporter, Subfamily B, Member 1/*antagonists & inhibitors
Colorectal Neoplasms/*drug therapy
Fluorouracil/*pharmacology
Gene Expression Regulation, Neoplastic/*drug effects
NF-kappa B/*metabolism
S-Adenosylmethionine/*pharmacology
Antimetabolites, Antineoplastic/pharmacology ; Apoptosis ; Cell Proliferation ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Drug Synergism ; Drug Therapy, Combination ; Humans ; NF-kappa B/genetics ; Tumor Cells, Cultured
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References:
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Contributed Indexing:
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Keywords: 5-Fluorouracil; P-glycoprotein; S-Adenosylmethionine; colorectal cancer; combination therapy; multidrug resistance
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Substance Nomenclature:
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0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
0 (Antimetabolites, Antineoplastic)
0 (NF-kappa B)
7LP2MPO46S (S-Adenosylmethionine)
U3P01618RT (Fluorouracil)
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Entry Date(s):
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Date Created: 20210910 Date Completed: 20211018 Latest Revision: 20211018
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Update Code:
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20240105
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PubMed Central ID:
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PMC8431578
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DOI:
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10.3390/ijms22179286
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PMID:
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34502219
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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 116 p53+/+ 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.