Aloe-emodin-mediated photodynamic therapy induces autophagy and apoptosis in human osteosarcoma cell line MG-63 through the ROS/JNK signaling pathway

• Published in: Oncology reports Vol. 35; no. 6; pp. 3209 - 3215
• Main Authors: TU, PINGHUA, HUANG, QIU, OU, YUNSHENG, DU, XING, LI, KAITING, TAO, YONG, YIN, HANG
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.06.2016; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Acetylcysteine - pharmacology; aloe-emodin; Anthracenes - pharmacology; Anthraquinones - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis Regulatory Proteins - metabolism; Autophagy; Autophagy (Cytology); Autophagy - drug effects; Bone cancer; Bone Neoplasms - drug therapy; Bone Neoplasms - pathology; Cancer; Care and treatment; Cell Line, Tumor; Cell Survival - drug effects; Cellular signal transduction; Chinese medicine; Drug Screening Assays, Antitumor; Flow cytometry; Health aspects; Humans; JNK Mitogen-Activated Protein Kinases - metabolism; MAP Kinase Signaling System; Methods; Osteosarcoma; Osteosarcoma - drug therapy; Osteosarcoma - pathology; Patient outcomes; Photochemotherapy; Photodynamic therapy; Photosensitizing Agents - pharmacology; Proteins; Reactive Oxygen Species - metabolism; Sarcoma; Studies; Tumors; United States > US
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2016.4703

The present study was carried out to investigate the effect and mechanisms of aloe-emodin (AE)-mediated photodynamic therapy (AE-PDT) on the human osteosarcoma cell line MG-63. After treatment with AE-PDT, the human osteosarcoma cell line MG-63 was tested for levels of viability, autophagy, reactive oxygen species (ROS) and apoptosis and changes in cell morphology with the Cell Counting Kit-8 (CCK-8), monodansylcadaverine (MDC) and Hoechst staining and transmission electron microscopy. The expression of proteins including LC-3, cleaved caspase-3, Beclin-1, Bcl-2, p-JNK, t-JNK and β-actin was examined with western blotting. AE-PDT significantly inhibited the viability of the MG-63 cells in an AE-concentration- and PDT energy density-dependent manner. Autophagy and apoptosis of MG-63 cells was substantially promoted in the AE-PDT group compared to the control group, the AE alone group and the light emitting diode (LED) alone group. Inhibition of autophagy by 3-meth-yladenine (3-MA) (5 mM) and chloroquine (CQ) (15 µM) significantly promoted the apoptosis rate and improved the sensitivity of the MG-63 cells to AE-PDT. AE-PDT was found to induce the expression of ROS and p-JNK. ROS scavenger, N-acetyl-L-cysteine (NAC, 5 mM), was able to hinder the autophagy, apoptosis and phosphorylation of JNK, and JNK inhibitor (SP600125, 10 µM) significantly inhibited the autophagy and apoptosis, and attenuated the sensitivity of MG63 cells to AE-PDT. In conclusion, AE-PDT induced the autophagy and apoptosis of human osteosarcoma cell line MG-63 through the activation of the ROS-JNK signaling pathway. Autophagy may play a protective role during the early stage following treatment of AE-PDT.