Ethanol extract of asiasari radix preferentially induces apoptosis in G361 human melanoma cells by differential regulation of p53
BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE
Authors: Park, Kwang-Ha; Choi, Jeong-Hae; Song, Yeon-Suk; Kim, Gyoo-Cheon; Hong, Jin-Woo
Abstract
Background In Korea and China, asiasari radix (AR) is widely used as a traditional anti-inflammatory and analgesic agent. After its skin-regenerating and hair loss-preventing activities were identified, several types of AR extracts were used for aesthetic purposes. Nevertheless, the effect of ARE on various types of skin cancers was not fully studied yet. Methods In this study, we tested the effect of an ethanolic AR extract (ARE) on G361 human melanoma and HaCaT human keratinocyte cell lines. After ARE exposure, cell growth and the expression patterns of proteins and genes were monitored. Results The ARE-mediated cell growth inhibition was greater in G361 cells than in HaCaT cells due to differences in its cell growth regulation effects. Interestingly, ARE treatment induced caspase-3-mediated apoptosis in G361 cells, but not in HaCaT cells. Furthermore, ARE reduced the expression of p53 and p21 proteins in G361 cells, whereas it induced their expression in HaCaT cells. ARE induced cell death in G361 cells through the reactive oxygen species (ROS)-dependent regulation of p53 and p21 in G361 cells. Microarray analysis showed that ARE regulates Mouse double minute 2 homolog (MDM2) and CASP8 and FADD-like apoptosis regulator (CFLAR) gene expression in G361 and HaCaT cells differently. Conclusion The treatment of ARE preferentially induces apoptosis in melanoma cells by the ROS-dependent differential regulation of p53 level. Therefore, ARE can be used as a new medicinal option for melanoma.
PM2.5 induces male reproductive toxicity via mitochondrial dysfunction, DNA damage and RIPK1 mediated apoptotic signaling pathway
SCIENCE OF THE TOTAL ENVIRONMENT
Authors: Zhang, Jin; Liu, Jianhui; Ren, Lihua; Wei, Jialiu; Duan, Junchao; Zhang, Lefeng; Zhou, Xianqing; Sun, Zhiwei
Abstract
Recent years, air pollution has been a serious problem, and PM2.5 is the main air particulate pollutant. Studies have investigated that PM2.5 is a risky factor to the deterioration of semen quality inmales. But, the related mechanismis still unclear. To explore the effect of PM2.5, Sprague Dawley (SD) rats were exposed to PM2.5 (0, 1.8, 5.4 and 16.2 mg/kg.bw.) through intratracheal instillation. The exposure was performed once every 3 days and continued for 30 days. In vitro, GC-2spd cells were treated using 0, 50, 100, 200 mu g/mL PM2.5 for 24 h. The data showed that sperm relative motility rates and density were remarkably decreased, while sperm malformation rates were significantly increased with exposure to the PM2.5. The expression of Fas/FasL/RIPK1/FADD/Caspase-8/Caspase-3 and the level of 8-OHdG expression in testes were significantly increased after exposure to PM2.5. Additionally, in vitro the results showed that PM2.5 inhibited cell viability, increased the release of lactate dehydrogenase (LDH) by increasing reactive oxygen species (ROS) level. And ROS induced-DNA damage led to cell cycle arrest at G0/G1 phases and proliferation inhibition. Similar to the vivo study, the expressions of Fas/FasL/RIPK1/FADD/Caspase-8/Caspase-3 in GC-2spd cells were significantly increased after exposure to PM2.5 for 24-h. In addition, PM2.5 decreased the levels of ATP by impairing mitochondria structures, which led to energy metabolism obstruction resulted in the decrease of sperm motility. The above three aspects together resulted in the decrease in sperm quantity and quality. (C) 2018 Elsevier B.V. All rights reserved.