Apoptosis and necrosis induced by novel realgar quantum dots in human endometrial cancer cells via endoplasmic reticulum stress signaling pathway

Huan Wang,1–3 Zhengyun Liu,4 Ying Gou,3 Yu Qin,4 Yaze Xu,5 Jie Liu,4 Jin-Zhu Wu6 1Research Center for Medicine and Biology, 2Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, 3Department of Microbiology, 4Key Lab for Basic Pharmacology of Ministry of Education, 5Pharmacy School, Zunyi Medical College, Zunyi, 6Department of Chemistry, School of Science, Harbin Institute of Technology, Harbin, People’s Republic of China 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 antiproliferative 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. Keywords: realgar, quantum dots, apoptosis, necrosis, endoplasmic reticulum stress, endometrial cancer cell