Untitled

Funder

Organizational Unit

Publications

The chemopreventive effect of the dietary compound kaempferol on the MCF-7 human breast cancer cell line is dependent on inhibition of glucose cellular uptake

Publication . Azevedo, Cláudia; Correia-Branco, Ana; Araújo, João R.; Guimarães, João T.; Keating, Elisa; Martel, Fátima

Our aim was to investigate the effect of several dietary polyphenols on glucose uptake by breast cancer cells. Uptake of H-3-deoxy-D-glucose (H-3-DG) by MCF-7 cells was time-dependent, saturable, and inhibited by cytochalasin B plus phloridzin. In the short-term (26min), myricetin, chrysin, genistein, resveratrol, kaempferol, and xanthohumol (10-100 mu M) inhibited H-3-DG uptake. Kaempferol was found to be the most potent inhibitor of H-3-DG uptake [IC50 of 4 mu M (1.6-9.8)], behaving as a mixed-type inhibitor. In the long-term (24h), kaempferol (30 mu M) was also able to inhibit H-3-DG uptake, associated with a 40% decrease in GLUT1 mRNA levels. Interestingly enough, kaempferol (100 mu M) revealed antiproliferative (sulforhodamine B and H-3-thymidine incorporation assays) and cytotoxic (extracellular lactate dehydrogenase activity determination) properties, which were mimicked by low extracellular (1mM) glucose conditions and reversed by high extracellular (20mM) glucose conditions. Finally, exposure of cells to kaempferol (30 mu M) induced an increase in extracellular lactate levels over time (to 731 +/- 32% of control after a 24 h exposure), due to inhibition of MCT1-mediated lactate cellular uptake. In conclusion, kaempferol potently inhibits glucose uptake by MCF-7 cells, apparently by decreasing GLUT1-mediated glucose uptake. The antiproliferative and cytotoxic effect of kaempferol in these cells appears to be dependent on this effect.

2015Journal article

Restricted access

Modulation of the uptake of critical nutrients by breast cancer cells by lactate: Impact on cell survival, proliferation and migration

Publication . Guedes, Marta; Araújo, João R.; Correia-Branco, Ana; Gregório, Inês; Martel, Fátima; Keating, Elisa

This work aimed to characterize the uptake of folate and glucose by breast cancer cells and to study the effect of lactate upon the transport of these nutrients and upon cell viability, proliferation and migration capacity. Data obtained showed that: a) MCF7 cells uptake (3)H-folic acid ((3)H-FA) at physiological but not at acidic pH; b) T47D cells accumulate (3)H-FA and (14)C-5-methyltetrahydrofolate ((14)C-5-MTHF) more efficiently at acidic than at physiological pH; c) (3)H-deoxyglucose ((3)H-DG) uptake by T47D cells is sodium-independent, inhibited by cytochalasin B (CYT B) and stimulated by insulin. Regarding the effect of lactate, in T47D cells, acute (26 min) and chronic (24 h) exposure to lactic acid (LA) stimulated (3)H-FA uptake. Acute exposure to LA also stimulated (3)H-DG uptake and chronic exposure to LA significantly stimulated T47D cell migratory capacity. In conclusion, the transport of folates is strikingly different in two phenotypically similar breast cancer cell lines: MCF7 and T47D cells. Additionally, lactate seems to act as a signaling molecule which increases the uptake of nutrients and promotes the migration capacity of T47D cells.

2016Journal article

Restricted access