Resveratrol inhibits plasma membrane Ca2+-ATPase inducing an increase in cytoplasmic calcium

• Resveratrol induces a rise in [Ca2+]i via plasma membrane Ca2+-ATPase inhibition.
• FURA-2 is compatible with resveratrol in measuring [Ca2+]i.
• PMCA inhibition is novel to resveratrol among naturally occurring polyphenols.

Plasma membrane Ca2+-ATPase (PMCA) plays a vital role in maintaining cytosolic calcium concentration ([Ca2+]i). Given that many diseases have modified PMCA expression and activity, PMCA is an important potential target for therapeutic treatment. This study demonstrates that the non-toxic, naturally-occurring polyphenol resveratrol (RES) induces increases in [Ca2+]i via PMCA inhibition in primary dermal fibroblasts and MDA-MB-231 breast cancer cells. Our results also illustrate that RES and the fluorescent intracellular calcium indicator Fura-2, are compatible for simultaneous use, in contrast to previous studies, which indicated that RES modulates the Fura-2 fluorescence independent of calcium concentration. Because RES has been identified as a PMCA inhibitor, further studies may be conducted to develop more specific PMCA inhibitors from RES derivatives for potential therapeutic use.