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Calyculin A From Discodermia Calyx Is a Dual Action Toxin That Blocks Calcium Influx and Inhibits Protein Ser/Thr Phosphatases

Calyculin A From Discodermia Calyx Is a Dual Action Toxin That Blocks Calcium Influx and Inhibits Protein Ser/Thr Phosphatases

Maja Holy, David L Brautigan

Toxins (Basel). 2012 Oct;4(10):940-54.

PMID: 23162706

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP101932712	Calyculin A from Discodermia calyx		101932-71-2	Price

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