Mitochondria-Associated Apoptosis in Human Melanoma Cells Induced by Cardanol Monoene from Cashew Nut Shell Liquid

• Published in: Journal of agricultural and food chemistry 2017-07, Vol.65 (28), p.5620-5631
• Main Authors: Su, Wei-Chao, Lin, Yu-Feng, Yu, Xiang-Ping, Wang, Yu-Xia, Lin, Xiao-Dong, Su, Qiao-Zhen, Shen, Dong-Yan, Chen, Qing-Xi
• Format: Article
• Language: English
• Subjects: Anacardium - chemistry; Apoptosis - drug effects; bcl-2-Associated X Protein - metabolism; Caspase 3 - genetics; Caspase 3 - metabolism; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; Cytochromes c - metabolism; Humans; Melanoma - drug therapy; Melanoma - genetics; Melanoma - metabolism; Melanoma - physiopathology; Mitochondria - drug effects; Mitochondria - metabolism; Nuts - chemistry; Phenols - pharmacology; Plant Extracts - pharmacology; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.7b01381

Cardanol monoene (CM) is the major phenolic component extracted from cashew nut shell liquid (CNSL), which has been relevant to wide range of biological effects. In this study, we found that CM could inhibit the M14 human melanoma cells proliferation in a dose dependent and time dependent manner, and the IC50 values were determined to be 23.15 ± 2.42 μM and 12.30 ± 1.67 μM after 24 and 48 h treatment, respectively. The flow cytometric analysis demonstrated that CM induced M14 cell cycle arrest at the S phase, along with the collapse of mitochondrial membrane potential (ΔΨm) and the accumulation of reactive oxygen species (ROS) level in cells, but the apoptotic cells reduced when treated with Z-VAD-FMK (pan-caspase inhibitor). Western blotting showed that the expressions of p53, cytosol cytochrome C, cleaved-caspase-3, and cleaved-PARP were up-regulated, and the expression level of Bax/Bcl-2 ratio increased significantly. The 2527 significant differentially expressed genes were obtained by RNA-seq, which were assigned to 270 KEGG pathways. These results indicated that CM induced M14 cells apoptosis via the ROS triggered mitochondrial-associated pathways, which supports the potential application of CM for the therapy of melanoma cancer.