Inhibition of Glutamine Cellular Uptake Contributes to the Cytotoxic Effect of Xanthohumol in Triple-Negative Breast Cancer Cells

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Carmo, F (Author) Other; Silva, C (Author) FMUP; Martel, F (Author) FMUP

Journal

Title: Nutrition and Cancer

Vol. 74

Pages: 3413-3430

ISSN: 0163-5581

Publisher: Taylor & Francis

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 5 Citations

Other information

Authenticus ID: P-00W-ND6

DOI: 10.1080/01635581.2022.2076889

Abstract (EN): Breast cancer constitutes the most incident cancer and one of the most common causes of cancer-related death. Glutamine addiction, an important metabolic feature of cancer cells, is dependent on supply of this amino acid from external sources. In this study, the effect of several polyphenols (catechin, epicatechin, EGCG, catechin:lysine, naringenin, hesperidin, malvidin, delphinidin, kaempferol, quercetin, rutin, myricetin, resveratrol, xanthohumol, and chrysin) upon glutamine (H-3-GLN) uptake by human breast epithelial adenocarcinoma cell lines with distinct characteristics (MCF-7 and MDA-MB-231) was assessed. Several polyphenols interfere with H-3-GLN uptake by both cell lines. Xanthohumol markedly decreases total and Na+-dependent H-3-GLN uptake and showed a cytotoxic and anti-proliferative effect in MDA-MB-231 cells. Xanthohumol is as an uncompetitive inhibitor of Na+-dependent H-3-GLN uptake and inhibits GPNA (L-gamma-glutamyl-p-nitroanilide)-sensitive, both ASCT2 (alanine, serine, cysteine transporter 2)-mediated and non-ASCT2-mediated H-3-GLN uptake. Xanthohumol does not interfere with the transcription rates of ASCT2. The cytotoxic effect of xanthohumol, but not its anti-proliferative effect, is GPNA-sensitive and related to ASCT2 inhibition. Combination of xanthohumol with the breast cancer chemotherapeutic agent doxorubicin results in an additive anti-proliferative, but not cytotoxic effect. We conclude that targeting glutamine uptake might constitute a potential interesting strategy for triple-negative breast cancer.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 18