title: Thioredoxin-1 inhibitor, 1-methylpropyl 2-imidazolyl disulfide, inhibits the growth, migration and invasion of colorectal cancer cell lines.
abstract: 1-Methylpropyl 2-imidazolyl disulfide (PX-12) has been proposed as an inhibitor of thioredoxin-1 (Trx-1) with antitumor activity. However, the antitumor activity of the Trx-1 redox signaling inhibitor PX-12 on colorectal cancer is still obscure. In the present study, we showed that PX-12 inhibited the growth of colorectal cancer DLD-1 and SW620 cells in a dose- and time-dependent manner. Further analysis demonstrated that PX-12 reduced cell colony formation and induced a G2/M phase arrest of the cell cycle. In addition, PX-12 treatment induced apoptosis, as observed by the increased number of Annexin V-positive cells and increased activation of caspase-3. Notably, a low dose of PX-12 inhibited colorectal cancer cell migration and invasion. Treatment of cancer cells with PX-12 reduced NOX1, CDH17 and S100A4 mRNA expression, and increased KLF17 mRNA expression. Moreover, PX-12 decreased S100A4 protein expression in the colorectal cancer cells. Collectively, the present study demonstrates the antitumor effects and therapeutic potential of PX-12 in colorectal cancer.
authors.affiliation: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Fule
authors.initials: F
authors.lastname: Wang
authors.affiliation: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Feiyan
authors.initials: F
authors.lastname: Lin
authors.affiliation: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Peili
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Reproductive Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Wuhua
authors.initials: W
authors.lastname: Ni
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Laixi
authors.initials: L
authors.lastname: Bi
authors.affiliation: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wu
authors.affiliation: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
mesh_terms: D017304:Annexin A5 / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D004220:Disulfides / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013879:Thioredoxins / Q000037:antagonists & inhibitors*
chemical_list: D017304:Annexin A5; D000970:Antineoplastic Agents; D004220:Disulfides; D007093:Imidazoles; D012333:RNA, Messenger; C491203:TXN protein, human; D013879:Thioredoxins; C412893:1-methylpropyl-2-imidazolyl disulfide; C505407:CASP3 protein, human; D053148:Caspase 3