title: A novel benzothiazole derivative YLT322 induces apoptosis via the mitochondrial apoptosis pathway in vitro with anti-tumor activity in solid malignancies.
abstract: Benzothiazole derivatives are known for various biological activities, and their potency in cancer therapy has received considerable attention in recent years. YLT322, a novel synthesized benzothiazole derivative, exhibits potent anti-tumor activity via inducing apoptosis both in vitro and in vivo. In this study, we found that YLT322 showed growth inhibition against a broad spectrum of human cancer cells and induced apoptosis of HepG2 cells in a dose- and time-dependent manner. The occurrence of its apoptosis was associated with activation of caspases-3 and -9, but not caspase-8. YLT322 increased the expression of Bax, decreased the expression of Bcl-2, and induced the release of cytochrome c which activates the mitochondrial apoptotic pathway. The down-regulation of phosphorylated p42/44 MAPK and phosphorylated Akt was also observed. Moreover, YLT322 suppressed the growth of established tumors in xenograft models in mice without obvious side effects. Histological and immunohistochemical analyses revealed an increase in TUNEL and caspase-3-positive cells and a decrease in Ki67-positive cells upon YLT322. These results suggest that YLT322 may be a potential candidate for cancer therapy.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Song
authors.initials: S
authors.lastname: Xuejiao
authors.forename: Xia
authors.initials: X
authors.lastname: Yong
authors.forename: Wang
authors.initials: W
authors.lastname: Ningyu
authors.forename: Zhang
authors.initials: Z
authors.lastname: Lidan
authors.forename: Shi
authors.initials: S
authors.lastname: Xuanhong
authors.forename: Xu
authors.initials: X
authors.lastname: Youzhi
authors.forename: Ye
authors.initials: Y
authors.lastname: Tinghong
authors.forename: Shi
authors.initials: S
authors.lastname: Yaojie
authors.forename: Zhu
authors.initials: Z
authors.lastname: Yongxia
authors.forename: Yu
authors.initials: Y
authors.lastname: Luoting
mesh_terms: D000631:Aminopyridines / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D052160:Benzothiazoles / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C585526:2-chloro-N-(2-(2-(5-methylpyridin-2-ylamino)-2-oxoethylthio)benzo(d)thiazol-6-yl) acetamide; D000631:Aminopyridines; D000970:Antineoplastic Agents; D052160:Benzothiazoles; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; C005465:benzothiazole