title: Apoptosis and necrosis induced by novel realgar quantum dots in human endometrial cancer cells via endoplasmic reticulum stress signaling pathway.
abstract: Realgar (AS4S4) has been used in traditional medicines for malignancy, but the poor water solubility is still a major hindrance to its clinical use. Realgar quantum dots (RQDs) were therefore synthesized with improved water solubility and bioavailability. Human endometrial cancer JEC cells were exposed to various concentrations of RQDs to evaluate their anticancer effects and to explore mechanisms by the MTT assay, transmission electron microscopy (TEM), flow cytometry, real-time reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis. Results revealed that the highest photoluminescence quantum yield of the prepared RQDs was up to approximately 70%, with the average size of 5.48 nm. RQDs induced antipro-liferative activity against JEC cells in a concentration-dependent manner. In light microscopy and TEM examinations, RQDs induced vacuolization and endoplasmic reticulum (ER) dilation in JEC cells in a concentration-dependent manner. ER stress by RQDs were further confirmed by increased expression of GADD153 and GRP78 at both mRNA and protein levels. ER stress further led to JEC cell apoptosis and necrosis, as evidenced by flow cytometry and mitochondrial membrane potential detection. Our findings demonstrated that the newly synthesized RQDs were effective against human endometrial cancer cells. The underlying mechanism appears to be, at least partly, due to ER stress leading to apoptotic cell death and necrosis.
authors.affiliation: Research Center for Medicine and Biology, Zunyi Medical College, Zunyi, People's Republic of China ; Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical College, Zunyi, People's Republic of China ; Department of Microbiolog, Zunyi Medical College, Zunyi, People's Republic of China y.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Lab for Basic Pharmacology of Ministry of Education, Zunyi Medical College, Zunyi, People's Republic of China.
authors.forename: Zhengyun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Microbiolog, Zunyi Medical College, Zunyi, People's Republic of China y.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gou
authors.affiliation: Key Lab for Basic Pharmacology of Ministry of Education, Zunyi Medical College, Zunyi, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Pharmacy School, Zunyi Medical College, Zunyi, People's Republic of China.
authors.forename: Yaze
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Key Lab for Basic Pharmacology of Ministry of Education, Zunyi Medical College, Zunyi, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Chemistry, School of Science, Harbin Institute of Technology, Harbin, People's Republic of China.
authors.forename: Jin-Zhu
authors.initials: JZ
authors.lastname: Wu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001152:Arsenicals; D045744:Cell Line, Tumor / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D046529:Microscopy, Electron, Transmission; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology*; D045663:Quantum Dots / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013440:Sulfides / Q000633:toxicity*; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism
chemical_list: D001152:Arsenicals; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D013440:Sulfides; D051742:Transcription Factor CHOP; C058317:arsenic disulfide
keywords: apoptosis; endometrial cancer cells; endoplasmic reticulum stress; necrosis; quantum dots; realgar