Gamma irradiation of aloe-emodin induced structural modification and apoptosis through a ROS- and caspase-dependent mitochondrial pathway in stomach tumor cells. (7th March 2018)

• Record Type: Journal Article
• Authors: Byun, Eui-Baek; Kim, Hye-Min; Sung, Nak-Yun; Yang, Mi-So; Kim, Woo Sik; Choi, DaeSeong; Mushtaq, Sajid; Lee, Seung Sik; Byun, Eui-Hong
• Is Part Of: International journal of radiation biology. Volume 94:Number 4(2018)
• Page Start: 403
• Page End: 416
• Publication Date: 2018-03-07
• Subjects: Gamma irradiation -- aloe-emodin -- structural modification -- cytotoxicity -- apoptosis; Radiation -- Physiological effect -- Periodicals; Radiobiology -- Periodicals; 571.45
• DOI: 10.1080/09553002.2018.1440330
• Languages: English
• ISSNs: 0955-3002

Abstract

Abstract: Purpose: The changes in molecular structure and the physiological properties of a gamma-irradiated aloe-emodin were examined. Materials and methods: Aloe-emodin was gamma-irradiated at doses ranging from 0 to 150 kGy, and the molecular structure was then analyzed using high-performance liquid chromatography (HPLC). AGS cells were cultured in RPMI medium and treated gamma irradiated aloe-emodin. Cell viability was measured by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Apoptosis efficiency was investigated by cell cycle arrest, cell morphology, and signaling pathway. The structure of new radiolytic peak was identified by the hydrogen-nuclear magnetic resonance ( 1 H NMR). Results: HPLC results showed that gamma irradiation induced new radiolytic peaks that were distinguishable from the aloe-emodin standard, and the area of new peaks was increased as the radiation dose increased. Gamma-irradiated aloe-emodin treatment significantly increased the cytotoxicity in AGS tumor cells. We also found that 150 kGy aloe-emodin increased the expression of Bax, cytosolic cytochrome c, PARP cleavage, and the activation of caspases-8, -9, -3, Bid, and Bcl-2. Treatment of 150 kGy aloe-emodin induced ROS production, DNA fragmentation, alterations of cell morphology, and the migration in AGS cells. Gamma-irradiated aloe-emodin induced an increase of sub-G1 phase and depolarization of mitochondrial membrane potential in AGS cells. We also confirmed that fractionated AEF1 (new radiolytic peak) induce the cell death, migration, an increase of sub-G1 phase and cytochrome c in a ROS-dependent manner. Conclusions: The radiolysis product (AEF1) of aloe-emodin transformed by gamma-irradiation strongly induced apoptotic cell death in AGS cells, indicating AEF1 is a potential candidate drug for use in anti-cancer drug.