ATP2A3 gene as an important player for resveratrol anticancer activity in breast cancer cells

The Ca 2+ ‐ATPases from the Sarco/endoplasmic reticulum (SERCA) are fundamental for maintaining intracellular [Ca 2+ ] homeostasis by pumping Ca 2+ 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 Ca 2+ levels, as well as changes in the capacity for Ca 2+ 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.