{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T03:20:20Z","timestamp":1784949620442,"version":"3.55.0"},"reference-count":29,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2012,10,22]],"date-time":"2012-10-22T00:00:00Z","timestamp":1350864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Calyculin A (Caly A) is cell permeable toxin widely used in cell biology research as an inhibitor of type 1 and type 2A protein Ser\/Thr phosphatases of the PPP family. Here we tested effects of low concentrations of Caly A on proliferation of human cancer and non-cancer cell lines. We found that long-term 0.3 nM Caly A prevented G1 to S phase cell cycle progression in human Hs-68 fibroblasts and ARPE19 epithelial cells, but not human breast cancer MDA-MB-468, MDA-MB-231 and MCF7 cells. These conditions produced no change in cyclin D1 levels or in the phosphorylation of endogenous proteins. However, acute application of 0.3 nM Caly A blocked serum-induced increase in intracellular calcium levels in Hs-68 fibroblasts, but not in MDA-MB-468 breast cancer cells. We propose that subnanomolar Caly A prevents cell cycle progression because it blocks calcium uptake by fibroblasts. This probably involves non-selective cation channels and cancer cell proliferation was not affected because calcium enters these cells by other channels. Our results suggest that calyculin A has dual actions and acts as a channel blocker, in addition to its well-established effects as a phosphatase inhibitor.<\/jats:p>","DOI":"10.3390\/toxins4100940","type":"journal-article","created":{"date-parts":[[2012,10,22]],"date-time":"2012-10-22T11:27:55Z","timestamp":1350905275000},"page":"940-954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Calyculin A from Discodermia Calyx Is a Dual Action Toxin that Blocks Calcium Influx and Inhibits Protein Ser\/Thr Phosphatases"],"prefix":"10.3390","volume":"4","author":[{"given":"Maja","family":"Holy","sequence":"first","affiliation":[{"name":"Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, VA 22908, USA"},{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Brautigan","sequence":"additional","affiliation":[{"name":"Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, VA 22908, USA"},{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2012,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1021\/ja00270a061","article-title":"Calyculin A, a novel antitumor metabolite from the marine sponge Discodermia. 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