Pei-Ying Chang1, Fuu-Jen Tsai2, Da-Tian Bau3, Yuan-Man Hsu4, Jai-Sing Yang5, Ming-Gene Tu6, Shang-Lun Chiang7. 1. Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; School of Dentistry, China Medical University, Taichung, Taiwan. 2. School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; China Medical University Children's Hospital, China Medical University, Taichung, Taiwan. 3. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan. 4. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan. 5. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan. 6. School of Dentistry, China Medical University, Taichung, Taiwan; Department of Dentistry, China Medical University Hospital, Taichung, Taiwan. Electronic address: mgtu@mail.cmu.edu.tw. 7. Environment-Omics-Disease Research Center, China Medical University Hospital, Taichung, Taiwan; Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan. Electronic address: chimpanzee99999@gmail.com.
Abstract
BACKGROUND/ PURPOSE: Cisplatin-resistant oral cancer is clinically difficult to manage and the dose-dependent toxicities of cisplatin has been widely concerned. Allyl isothiocyanate (AITC), known as mustard oil, is a plant-derived compound abundant in cruciferous vegetables. It is reported to have anti-cancer potential as a natural dietary chemopreventive compound against a variety of cancers, but the effect of AITC on cisplatin-resistant cancer cells is still little-known. METHODS: Human CAL27-cisplatin-resistant oral cancer cells (CAR cells) were examined to investigate the antitumor properties of AITC. 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay, IncuCyte™ S3 cell proliferation assay, 4',6-diamidino-2-phenylindole (DAPI) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining as well as Western blot analysis were deployed. RESULTS: AITC decreased CAR cell viability, induced cell death of CAR cells and inhibited the confluences of cultured CAR cells. When CAR cells were treated with AITC, activation of caspase-3 and caspase-9 by AITC was observed and could be reversed by Z-VAD-fmk (pan-caspase inhibitor). Furthermore, the protein expressions of phosphorylated protein kinase B (p-AKT) and phosphorylated mammalian target of rapamycin (p-mTOR) were suppressed in AITC-treated CAR cells, whereas protein expressions of Bax, cytochrome c, Apaf-1, cleaved caspase-3, and cleaved caspase-9 were upregulated in AITC-treated CAR cells. CONCLUSION: AITC can inhibit Akt/mTOR proliferation signaling and promote mitochondria-dependent apoptotic pathway through AITC-enhanced activities of caspase-3 and caspase-9 in CAR cells.
BACKGROUND/ PURPOSE:Cisplatin-resistant oral cancer is clinically difficult to manage and the dose-dependent toxicities of cisplatin has been widely concerned. Allyl isothiocyanate (AITC), known as mustard oil, is a plant-derived compound abundant in cruciferous vegetables. It is reported to have anti-cancer potential as a natural dietary chemopreventive compound against a variety of cancers, but the effect of AITC on cisplatin-resistant cancer cells is still little-known. METHODS:Human CAL27-cisplatin-resistant oral cancer cells (CAR cells) were examined to investigate the antitumor properties of AITC. 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay, IncuCyte™ S3 cell proliferation assay, 4',6-diamidino-2-phenylindole (DAPI) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining as well as Western blot analysis were deployed. RESULTS:AITC decreased CAR cell viability, induced cell death of CAR cells and inhibited the confluences of cultured CAR cells. When CAR cells were treated with AITC, activation of caspase-3 and caspase-9 by AITC was observed and could be reversed by Z-VAD-fmk (pan-caspase inhibitor). Furthermore, the protein expressions of phosphorylated protein kinase B (p-AKT) and phosphorylated mammalian target of rapamycin (p-mTOR) were suppressed in AITC-treated CAR cells, whereas protein expressions of Bax, cytochrome c, Apaf-1, cleaved caspase-3, and cleaved caspase-9 were upregulated in AITC-treated CAR cells. CONCLUSION:AITC can inhibit Akt/mTOR proliferation signaling and promote mitochondria-dependent apoptotic pathway through AITC-enhanced activities of caspase-3 and caspase-9 in CAR cells.
Authors: Jochen Rutz; Sebastian Maxeiner; Timothy Grein; Marlon Sonnenburg; Salma El Khadir; Nino Makhatelashvili; Johanna Mann; Hui Xie; Jindrich Cinatl; Anita Thomas; Felix K-H Chun; Axel Haferkamp; Roman A Blaheta; Igor Tsaur Journal: Int J Mol Sci Date: 2022-09-20 Impact factor: 6.208