1. Resveratrol derivatives increase cytosolic calcium by inhibiting plasma membrane ATPase and inducing calcium release from the endoplasmic reticulum in prostate cancer cells
- Author
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Colton M. Crowther, Merritt B. Andrus, Joshua Allen Peterson, and Jason Kenealey
- Subjects
PIV, 4′-pivalate resveratrol ,TG, thapsigargin ,0301 basic medicine ,DMEM, Dulbecco's modified Eagle medium ,PMCA, plasma membrane Ca2+-ATPase ,HBSS, Ca2+- and Mg2+-free Hank's Balanced Salt Solution ,ATPase ,IP3R, inositol triphosphate receptor ,DMSO, dimethyl sulfoxide ,Resveratrol ,Biochemistry ,PIP2, phosphatidylinositol biphosphate ,AUC, area under the curve ,chemistry.chemical_compound ,0302 clinical medicine ,lcsh:QD415-436 ,lcsh:QH301-705.5 ,Calcium signaling ,Prostate cancer ,biology ,MTT, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ,Cell biology ,030220 oncology & carcinogenesis ,Fura-2 ,IP3, inositol triphosphate ,PBS, phosphate-buffered saline ,Biophysics ,chemistry.chemical_element ,Calcium ,BuRV, 4′-butyrate resveratrol ,Article ,ER, endoplasmic reticulum ,lcsh:Biochemistry ,Plasma membrane Ca2+-ATPase ,Fura-2, Fura-2-Acetoxymethyl ester ,03 medical and health sciences ,PLC, phospholipase C ,FBS, fetal bovine serum ,2-APB, 2-Aminoethyl diphenylborinate ,Calcium metabolism ,Endoplasmic reticulum ,IsoRV, 4′-isobutyrate resveratrol ,[Ca2+]i, cytosolic calcium concentration ,030104 developmental biology ,chemistry ,lcsh:Biology (General) ,RES, resveratrol ,biology.protein ,Plasma membrane Ca2+ ATPase ,SERCA, sarcoendoplasmic reticular Ca2+-ATPase - Abstract
Resveratrol (RES) is a putative chemotherapeutic naturally found in grapes, peanuts, and Japanese knotweed. Previous studies demonstrate that RES modulates calcium signaling as part of its chemotherapeutic activity. In this study, we determined the chemotherapeutic activity of three RES esters that have been modified at the 4’ hydroxyl by the addition of pivalate, butyrate, and isobutyrate. All of the RES derivatives disrupted the calcium signaling in prostate cancer cells more than the parent compound, RES. Further, we demonstrate that the RES derivatives may disrupt the calcium homeostasis by activating calcium release from the endoplasmic reticulum and inhibiting plasma membrane Ca2+-ATPase. The pivalated and butyrated RES derivatives decreased cell viability significantly more than RES. Because pivalated and butyrated RES are more effective than RES at targeting calcium signaling pathways, pivalated and butyrated RES may serve as more effective chemotherapeutics., Highlights • Resveratrol (RES) derivatives increase [Ca2+]i more than RES in PC-3 cancer cells. • RES derivatives induce ER Ca2+ release to elevate [Ca2+]i. • RES derivatives inhibit plasma membrane Ca2+-ATPase to elevate [Ca2+]i. • RES derivatives decrease cell viability more than RES in PC-3 cancer cells.
- Published
- 2019