ATP2A3 gene as an important player for resveratrol anticancer activity in breast cancer cells.
The Ca2+-ATPases from the Sarco/endoplasmic reticulum (SERCA) are fundamental for maintaining intracellular [Ca2+] homeostasis by pumping Ca2+into the endoplasmic reticulum (ER) of eukaryotic cells. SERCA enzymes are encoded by three different genes (ATP2A1-3), whose expression occurs in a tissue and development stage-specific manner. It has been reported alterations in the expression of SERCA2 and SERCA3 pumps in different types of cancer: oral, lung, colon, stomach, central nervous system, thyroid, breast, and prostate. Resveratrol (RSV), a phytoalexin produced by a wide variety of plants in response to stress situations can modulate cellular processes involved in all stages of carcinogenesis. In this work, we used breast cancer cell lines (MCF-7 and MDA-MB-231) to evaluate mRNA levels of ATP2A2 and ATP2A3 genes in response to RSV treatment. Our results demonstrate that RSV treatment induced the expression of ATP2A3 gene in both cell lines in a time and concentration-dependent manner, while the expression of ATP2A2 gene remained unaffected. The RSV-induced expression of SERCA3 in these breast cancer cell lines produced decreased cell viability, triggered apoptosis and changes in cytosolic Ca2+levels, as well as changes in the capacity for Ca2+release by the ER. These data suggest an important participation of SERCA3 genes in RSV-mediated anti-tumor effect in breast cancer cell lines. Nevertheless, further research is needed to elucidate the molecular mechanisms underlying this effect.
Department of Biochemistry, School of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
Eduardo
E
Izquierdo-Torres
Department of Biochemistry, School of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
Gabriela
G
Rodríguez
Department of Biochemistry, School of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
Iván
I
Meneses-Morales
Department of Biochemistry, School of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
Angel
A
Zarain-Herzberg
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics; D000077185:Resveratrol; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D034741:RNA, Small Interfering; D013267:Stilbenes; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; C506949:ATP2A3 protein, human; D000077185:Resveratrol; D002118:Calcium
SERCA; apoptosis; breast cancer cells; calcium; resveratrol