Differential Redox Regulation of Ca^sup 2+^ Signaling and Viability in Normal and Malignant Prostate Cells

In prostate cancer, reactive oxygen species (ROS) are elevated and ... signaling is impaired. Thus, several novel therapeutic strategies have been developed to target altered ROS and ... signaling pathways in prostate cancer. Here, we investigate alterations of intracellular ... and inhibition of ce...

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Bibliographic Details
Published in:Biophysical journal 2015-10, Vol.109 (7), p.1410
Main Authors: Holzmann, Christian, Kilch, Tatiana, Kappel, Sven, Dörr, Kathrin, Jung, Volker, Stöckle, Michael, Bogeski, Ivan, Peinelt, Christine
Format: Article
Language:English
Subjects:
Calcium
Cells
Molecules
Prostate cancer
Tissues
Tumors
Online Access:Get full text
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Summary:In prostate cancer, reactive oxygen species (ROS) are elevated and ... signaling is impaired. Thus, several novel therapeutic strategies have been developed to target altered ROS and ... signaling pathways in prostate cancer. Here, we investigate alterations of intracellular ... and inhibition of cell viability caused by ROS in primary human prostate epithelial cells (hPECs) from healthy tissue and prostate cancer cell lines (LNCaP, DU145, and PC3). In hPECs, LNCaP and DU145 ... induces an initial ... increase, which in prostate cancer cells is blocked at high concentrations of ... Upon depletion of intracellular ... stores, store-operated ... entry (SOCE) is activated. SOCE channels can be formed by hexameric Orai1 channels; however, Orai1 can form heteromultimers with its homolog, Orai3. Since the redox sensor of Orai1 (Cys-195) is absent in Orai3, the Orai1/Orai3 ratio in T cells determines the redox sensitivity of SOCE and cell viability. In prostate cancer cells, SOCE is blocked at lower concentrations of ... compared with hPECs. An analysis of data from hPECs, LNCaP, DU145, and PC3, as well as previously published data from naive and effector ... cells, demonstrates a strong correlation between the Orai1/Orai3 ratio and the SOCE redox sensitivity and cell viability. Therefore, our data support the concept that store-operated ... channels in hPECs and prostate cancer cells are heteromeric Orai1/Orai3 channels with an increased Orai1/Orai3 ratio in cells derived from prostate cancer tumors. In addition, ROS-induced alterations in ... signaling in prostate cancer cells may contribute to the higher sensitivity of these cells to ROS. (ProQuest: ... denotes formulae/symbols omitted.)
ISSN:0006-3495
1542-0086