P-Glycoprotein 1 Affects Chemoactivities of Resveratrol against Human Colorectal Cancer Cells

• Published in: Nutrients Vol. 11; no. 9; p. 2098
• Main Authors: Aires, Virginie, Colin, Didier J, Doreau, Agnès, Di Pietro, Attilio, Heydel, Jean-Marie, Artur, Yves, Latruffe, Norbert, Delmas, Dominique
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04.09.2019; MDPI
• Subjects: ABC transporters; Affinity; Apoptosis; Apoptosis - drug effects; ATP Binding Cassette Transporter, Subfamily B - genetics; ATP Binding Cassette Transporter, Subfamily B - metabolism; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism; ATP-Binding Cassette Transporters - metabolism; Bioavailability; Biotechnology; Breast cancer; Cancer therapies; Cell cycle; Cell Line, Tumor; Cell proliferation; Cell Survival - drug effects; Chemotherapy; Cloning; Colon; Colon cancer; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - metabolism; Cyclosporins; Cytotoxicity; Drug Resistance, Neoplasm; Efflux; Endocytosis; Enzyme Inhibitors - metabolism; Enzyme Inhibitors - pharmacology; Flavonoids; Food and Nutrition; Gene Expression Regulation, Neoplastic - drug effects; Gene Silencing; Glycoproteins; Hepatocellular carcinoma; Humans; Immunoglobulins; Intestinal microflora; Kinases; Life Sciences; Metabolites; Microbiota; P-Glycoprotein; Pharmacokinetics; Polyphenols; Proteins; Resveratrol; Resveratrol - metabolism; Resveratrol - pharmacology; sensitivity; Substrates; Synergistic effect; transport; Tumor cell lines; France; ABC transporters; sensitivity; transport; resveratrol; colon cancer
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu11092098

Resveratrol has been proposed to prevent tumor growth and the different steps of carcinogenesis; nevertheless, these biological effects are sometimes discordant between different cell types. Several hypotheses and works have suggested that the metabolism of resveratrol could be at the origin of a different cellular response. We show here, using colorectal tumor cell lines, that the biological effects of RSV result mainly from its carriage by carriers of the superfamily of ABC transporter, i.e., P-gP, MRP, or BCRP. Using cell lines overexpressing these different transporters, we have been able to highlight the importance of P-gP in the response of cells to RSV. These results were confirmed by invalidating the gene coding for P-gP, which restored the sensitivity of colorectal cells resistant to the polyphenol. Subsequently, the status of P-glycoprotein expression is an important element to be taken into consideration in the cytotoxic activity of resveratrol in colorectal cancer cells.