PMID- 37966020 OWN - NLM STAT- MEDLINE DCOM- 20240208 LR - 20240208 IS - 1522-7278 (Electronic) IS - 1520-4081 (Linking) VI - 39 IP - 3 DP - 2024 Mar TI - Allyl isothiocyanate induces DNA damage and inhibits DNA repair-associated proteins in a human gastric cancer cells in vitro. PG - 1303-1314 LID - 10.1002/tox.24020 [doi] AB - Allyl isothiocyanate (AITC) is abundant in cruciferous vegetables and it present pharmacological activity including anticancer activity in many types of human cancer cells in vitro and in vivo. Currently, no available information to show AITC affecting DNA damage and repair-associated protein expression in human gastric cancer cells. Therefore, in the present studies, we investigated AITC-induced cytotoxic effects on human gastric cancer in AGS and SNU-1 cells whether or not via the induction of DNA damage and affected DNA damage and repair associated poteins expressions in vitro. Cell viability and morphological changes were assayed by flow cytometer and phase contrast microscopy, respectively, the results indicated AITC induced cell morphological changes and decreased total viable cells in AGS and SNU-1 cells in a dose-dependently. AITC induced DNA condensation and damage in a dose-dependently which based on the cell nuclei was stained by 4', 6-diamidino-2-phenylindole present in AGS and SNU-1 cells. DNA damage and repair associated proteins expression in AGS and SNU-1 cells were measured by Western blotting. The results indicated AITC decreased nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), glutathione, and catalase, but increased superoxide dismutase (SOD (Cu/Zn)), and nitric oxide synthase (iNOS) in AGS cells, however, in SNU-1 cells are increased HO-1. AITC increased DNA-dependent protein kinase (DNA-PK), phosphorylation of gamma H2A histone family member X on Ser139 (gammaH2AX(pSer139) ), and heat shock protein 90 (HSP90) in AGS cells. AITC increased DNA-PK, mediator of DNA damage checkpoint protein 1 (MDC1), gammaH2AX(pSer139) , topoisomerase II alpha (TOPIIalpha), topoisomerase II beta (TOPIIbeta), HSP90, and heat shock protein 70 (HSP70) in SNU-1 cells. AITC increased p53, p53(pSer15) , and p21 but decreased murine double minute 2 (MDM2)(pSer166) and O(6) -methylguanine-DNA methyltransferase (MGMT) in AGS cells; however, it has a similar effect of AITC except increased ataxia telangiectasia and Rad(3) -related protein (ATR)(pSer428) , checkpoint kinase 1 (CHK1), and checkpoint kinase 2 (CHK2) in SNU-1 cells. Apparently, both cell responses to AITC are different, nonetheless, all of these observations suggest that AITC inhibits the growth of gastric cancer cells may through induction off DNA damage in vitro. CI - (c) 2023 Wiley Periodicals LLC. FAU - Shih, Yung-Luen AU - Shih YL AD - School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan. AD - Department of Pathology and Laboratory Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. FAU - Hsu, Sheng-Yao AU - Hsu SY AD - Department of Ophthalmology, An Nan Hospital, China Medical University, Tainan, Taiwan. AD - Department of Optometry, Chung Hwa University of Medical Technology, Tainan, Taiwan. FAU - Lai, Kuang-Chi AU - Lai KC AD - Department of Surgery, School of Medicine, China Medical University, Taichung, Taiwan. AD - Department of Medical Laboratory Science and Biotechnology, College of Medical Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan. FAU - Chueh, Fu-Shin AU - Chueh FS AD - Department of Food Nutrition and Health Biotechnology, Asia University, Taichung, Taiwan. FAU - Huang, Yuan-Li AU - Huang YL AD - Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan. FAU - Kuo, Chao-Lin AU - Kuo CL AUID- ORCID: 0000-0002-7803-3019 AD - Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan. FAU - Chen, Yung-Liang AU - Chen YL AD - Department of Medical Laboratory Science and Biotechnology, Yuanpei University, Hsinchu, Taiwan. FAU - Chen, Chiung-Ju AU - Chen CJ AD - Department of Pathology and Laboratory Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. AD - Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan. FAU - Peng, Shu-Fen AU - Peng SF AUID- ORCID: 0000-0002-1792-0474 AD - Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. AD - Department of Biological Science and Technology, China Medical University, Taichung, Taiwan. FAU - Huang, Wen-Wen AU - Huang WW AUID- ORCID: 0000-0002-1131-3673 AD - Department of Biological Science and Technology, China Medical University, Taichung, Taiwan. FAU - Lu, Hsu-Fen AU - Lu HF AUID- ORCID: 0000-0003-4567-3754 AD - Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan. AD - Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan. LA - eng GR - CMU111-ASIA-13/China Medical University/ GR - 2023SKHAND009/Shin Kong Wu Ho-Su Memorial Hospital/ PT - Journal Article DEP - 20231115 PL - United States TA - Environ Toxicol JT - Environmental toxicology JID - 100885357 RN - 62414-75-9 (2,3,4-tri-O-acetylarabinopyranosyl isothiocyanate) RN - BN34FX42G3 (allyl isothiocyanate) RN - 0 (Tumor Suppressor Protein p53) RN - 0 (Isothiocyanates) RN - 9007-49-2 (DNA) SB - IM MH - Humans MH - Animals MH - Mice MH - *Tumor Suppressor Protein p53/genetics MH - *Stomach Neoplasms MH - DNA Damage MH - Isothiocyanates/pharmacology MH - DNA Repair MH - DNA MH - Cell Line, Tumor OTO - NOTNLM OT - AITC OT - DNA damage OT - DNA repair OT - allyl isothiocyanate OT - gastric cancer EDAT- 2023/11/15 12:43 MHDA- 2024/02/08 06:43 CRDT- 2023/11/15 07:23 PHST- 2023/09/07 00:00 [revised] PHST- 2023/03/28 00:00 [received] PHST- 2023/10/07 00:00 [accepted] PHST- 2024/02/08 06:43 [medline] PHST- 2023/11/15 12:43 [pubmed] PHST- 2023/11/15 07:23 [entrez] AID - 10.1002/tox.24020 [doi] PST - ppublish SO - Environ Toxicol. 2024 Mar;39(3):1303-1314. doi: 10.1002/tox.24020. Epub 2023 Nov 15.