Gene interactions and pathways from curated databases and text-mining
Oncogene 2009, PMID: 19701246

Dithiolethione compounds inhibit Akt signaling in human breast and lung cancer cells by increasing PP2A activity.

Switzer, C H; Ridnour, L A; Cheng, R Y S; Sparatore, A; Del Soldato, P; Moody, T W; Vitek, M P; Roberts, D D; Wink, D A

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.

Diseases/Pathways annotated by Medline MESH: Breast Neoplasms, Lung Neoplasms
Document information provided by NCBI PubMed

Text Mining Data

Akt ⊣ PP2A: " Dithiolethione compounds inhibit Akt signaling in human breast and lung cancer cells by increasing PP2A activity "

Akt ⊣ ACS-1: " Akt activation, as determined by serine-473 phosphorylation, was inhibited by ACS-1 in cells stimulated with either EGF or fibronectin "

mammalian target of rapamycin ⊣ ACS-1: " Furthermore, ACS-1 inhibited mammalian target of rapamycin signaling and decreased c-myc protein levels "

mammalian target of rapamycin ⊣ ACS-1: " Furthermore, ACS-1 inhibited mammalian target of rapamycin signaling and decreased c-myc protein levels "

PP2A → ACS-1: " ACS-1 did not proximally alter EGF receptor or integrin signaling, but caused a concentration dependent increase in PP2A activity "

Akt — ACS-1: " The effect of ACS-1 on Akt activation was not observed in the presence of the PP2A inhibitor okadaic acid "

PP2A — ACS-1: " ACS-1 effects on PP2A activity were independent of ARE activation and cAMP formation "

Manually curated Databases

No curated data.