Mechanisms of ATP-induced calcium signaling and growth arrest in human prostate cancer cells

• Published in: Cell calcium (Edinburgh) Vol. 34; no. 1; pp. 75 - 85
• Main Authors: Vanoverberghe, K., Mariot, P., Vanden Abeele, F., Delcourt, P., Parys, J.B., Prevarskaya, N.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier India Pvt Ltd 01.07.2003; Elsevier
• Subjects: Adenosine Triphosphate - metabolism; Adenosine Triphosphate - pharmacology; ATP; Calcium - metabolism; Calcium - pharmacology; Calcium Channels - drug effects; Calcium Channels - genetics; Calcium Channels - metabolism; Calcium signaling; Calcium Signaling - drug effects; Calcium Signaling - physiology; Cancer; Carcinoma - metabolism; Carcinoma - physiopathology; Cell Division - drug effects; Cell Division - physiology; Cell Line, Tumor; Cellular Biology; Cytoplasm - drug effects; Cytoplasm - metabolism; Down-Regulation - drug effects; Down-Regulation - physiology; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - metabolism; Growth arrest; Human health and pathology; Humans; Inositol 1,4,5-Trisphosphate Receptors; Intracellular Fluid - drug effects; Intracellular Fluid - metabolism; Life Sciences; Male; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - physiopathology; Protein Kinase C - metabolism; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Subcellular Processes; Thapsigargin - pharmacology; Type C Phospholipases - drug effects; Type C Phospholipases - metabolism; Urology and Nephrology; Calcium signaling; ATP; Growth arrest
• ISSN: 0143-4160; 1532-1991
• DOI: 10.1016/S0143-4160(03)00024-1

This study investigates the calcium mechanisms involved in growth arrest induced by extracellular ATP in DU-145 androgen-independent human prostate cancer cells. Exposure of DU-145 cells to 100 μM ATP produced an increase in cytoplasmic calcium concentration ([Ca 2+] i), due to a mobilization of calcium from the endoplasmic reticulum stores and to subsequent capacitative calcium entry (CCE). We have shown that this [Ca 2+] i increase occurs after stimulation by ATP of the phospholipase C (PLC) pathway. For the first time, we have identified the inositol 1,4,5-trisphosphate receptor (IP 3R) isoforms expressed in this cell line and have demonstrated a participation of protein kinase C in CCE. Using fluorescence imaging, we have shown that a long-term treatment with ATP leads to a decrease in the intraluminal endoplasmic reticulum calcium concentration as well as in the amount of releasable Ca 2+. Modulating extracellular free calcium concentrations indicated that variations in [Ca 2+] i did not affect the ATP-induced growth arrest of DU-145 cells. However, treating cells with 1 nM thapsigargin (TG) to deplete intracellular calcium pools prevented the growth arrest induced by ATP. Altogether, these results indicate that growth arrest induced in DU-145 cells by extracellular ATP is not correlated with an increase in [Ca 2+] i but rather with a decrease in intracellular calcium pool content.