Effects of camphorquinone on cytotoxicity, cell cycle regulation and prostaglandin E2 production of dental pulp cells: Role of ROS, ATM/Chk2, MEK/ERK and hemeoxygenase-1
Journal
PLoS ONE
Journal Volume
10
Journal Issue
12
Pages
e0143663
Date Issued
2015
Author(s)
Chang M.-C.
Wu M.-T.
Chan C.-P.
Sun T.-Y.
Jeng P.-Y.
Yeung S.-Y.
Lin H.-J.
Abstract
Camphorquinone (CQ) is a popularly-used photosensitizer in composite resin restoration. In this study, the effects of CQ on cytotoxicity and inflammation-related genes and proteins expression of pulp cells were investigated. The role of reactive oxygen species (ROS), ATM/Chk2/p53 and hemeoxygenase-1 (HO-1) and MEK/ERK signaling was also evaluated. We found that ROS and free radicals may play important role in CQ toxicity. CQ (1 and 2 mM) decreased the viability of pulp cells to about 70% and 50% of control, respectively. CQ also induced G2/M cell cycle arrest and apoptosis of pulp cells. The expression of type I collagen, cdc2, cyclin B, and cdc25C was inhibited, while p21, HO-1 and cyclooxygenase-2 (COX-2) were stimulated by CQ. CQ also activated ATM, Chk2, and p53 phosphorylation and GADD45α expression. Besides, exposure to CQ increased cellular ROS level and 8-isoprostane production. CQ also stimulated COX-2 expression and PGE2 production of pulp cells. The reduction of cell viability caused by CQ can be attenuated by N-acetyl-L-cysteine (NAC), catalase and superoxide dismutase (SOD), but can be promoted by Zinc protoporphyin (ZnPP). CQ stimulated ERK1/2 phosphorylation, and U0126 prevented the CQinduced COX-2 expression and prostaglandin E2 (PGE2) production. These results indicate that CQ may cause cytotoxicity, cell cycle arrest, apoptosis, and PGE2 production of pulp cells. These events could be due to stimulation of ROS and 8-isoprostane production, ATM/Chk2/p53 signaling, HO-1, COX-2 and p21 expression, as well as the inhibition of cdc2, cdc25C and cyclin B1. These results are important for understanding the role of ROS in pathogenesis of pulp necrosis and pulpal inflammation after clinical composite resin filling. ? 2015 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in anymedium, provided the original author and source are credited.
SDGs
Other Subjects
8 isoprostane; ATM protein; camphorquinone; catalase; checkpoint kinase 2; collagen type 1; cyclin B; cyclin dependent kinase 1; cyclooxygenase 2; growth arrest and DNA damage inducible protein 45; growth arrest and DNA damage inducible protein 45alpha; heme oxygenase 1; mitogen activated protein kinase; mitogen activated protein kinase 1; mitogen activated protein kinase 3; mitogen activated protein kinase kinase; prostaglandin E2; protein cdc25C; protein p21; protein p53; protein tyrosine phosphatase; reactive oxygen metabolite; superoxide dismutase; unclassified drug; 8-epi-prostaglandin F2alpha; ATM protein; ATM protein, human; camphor; camphorquinone; checkpoint kinase 2; CHEK2 protein, human; heme oxygenase 1; HMOX1 protein, human; prostaglandin E2; prostaglandin F2 alpha; reactive oxygen metabolite; Article; cell cycle progression; cell cycle regulation; cell viability; controlled study; cytotoxicity; G2 phase cell cycle checkpoint; human; human cell; prostaglandin synthesis; protein expression; protein phosphorylation; pulp necrosis; pulpitis; signal transduction; tooth disease; tooth pulp; adult; analogs and derivatives; apoptosis; biosynthesis; cell cycle checkpoint; cytology; drug effects; enzymology; metabolism; primary cell culture; young adult; Adult; Apoptosis; Ataxia Telangiectasia Mutated Proteins; Camphor; Cell Cycle Checkpoints; Checkpoint Kinase 2; Dental Pulp; Dinoprost; Dinoprostone; Heme Oxygenase-1; Humans; MAP Kinase Signaling System; Primary Cell Culture; Reactive Oxygen Species; Young Adult
Publisher
Public Library of Science
Type
journal article