Dithiolethione compounds inhibit Akt signaling in human breast and lung cancer cells by increasing PP2A activity
Articolo
Data di Pubblicazione:
2009
Citazione:
Dithiolethione compounds inhibit Akt signaling in human breast and lung cancer cells by increasing PP2A activity / C.H. Switzer, L.A. Ridnour, R.Y. Cheng, A. Sparatore, P. Del Soldato, T.W. Moody, M.P. Vitek, D.D. Roberts, D.A. Wink. - In: ONCOGENE. - ISSN 0950-9232. - 28:43(2009 Oct 29), pp. 3837-3843. [10.1038/onc.2009.244]
Abstract:
The chemopreventative effects of dithiolethione compounds are attributed to their activation of antioxidant response elements (AREs) by reacting with the Nrf2/Keap1 protein complex. In this study, we show antiproliferative effects of the dithiolethione compound ACS-1 in human cancer cell lines (A549 and MDA-MB-231) by increasing the activity of the tumor suppressor protein phoshatase 2A (PP2A). ACS-1 inhibited epidermal growth factor (EGF)-induced cellular proliferation in a concentration- and time-dependent manner. Akt activation, as determined by serine-473 phosphorylation, was inhibited by ACS-1 in cells stimulated with either EGF or fibronectin. Furthermore, ACS-1 inhibited mammalian target of rapamycin signaling and decreased c-myc protein levels. ACS-1 did not proximally alter EGF receptor or integrin signaling, but caused a concentration-dependent increase in PP2A activity. The effect of ACS-1 on Akt activation was not observed in the presence of the PP2A inhibitor okadaic acid. ACS-1 effects on PP2A activity were independent of ARE activation and cAMP formation. In addition to ACS-1, other dithiolethione compounds showed similar effects in reducing Akt activation, suggesting that this class of compounds may have other effects beyond chemoprevention
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Akt; Breast; Cancer; Dithiolethione; Lung; PP2A
Elenco autori:
C.H. Switzer, L.A. Ridnour, R.Y. Cheng, A. Sparatore, P. Del Soldato, T.W. Moody, M.P. Vitek, D.D. Roberts, D.A. Wink
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