A novel benzothiazole derivative YLT322 induces apoptosis via the mitochondrial apoptosis pathway in vitro with anti-tumor activity in solid malignancies

• Published in: PloS one Vol. 8; no. 5; p. e63900
• Main Authors: Xuejiao, Song, Yong, Xia, Ningyu, Wang, Lidan, Zhang, Xuanhong, Shi, Youzhi, Xu, Tinghong, Ye, Yaojie, Shi, Yongxia, Zhu, Luoting, Yu
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.05.2013; Public Library of Science (PLoS)
• Subjects: AKT protein; Aminopyridines - chemistry; Aminopyridines - pharmacology; Animal models; Animals; Anticancer properties; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor agents; Apoptosis; Apoptosis - drug effects; Bax protein; Bcl-2 protein; bcl-2-Associated X Protein - metabolism; Benzothiazole; Benzothiazoles - chemistry; Benzothiazoles - pharmacology; Biology; Cancer; Cancer therapies; Caspase; Caspase-3; Caspase-8; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemistry; Chemotherapy; Cytochrome; Cytochrome c; Cytochromes c - metabolism; Down-Regulation - drug effects; Female; Gene Expression Regulation, Neoplastic - drug effects; Growth inhibition; Humans; In vivo methods and tests; Kinases; Laboratories; Liver cancer; MAP kinase; Medical schools; Medicine; Membrane Potential, Mitochondrial - drug effects; Mice; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitogen-Activated Protein Kinases - metabolism; Phosphorylation - drug effects; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rodents; Side effects; Therapy; Tumors; Xenograft Model Antitumor Assays; Xenografts; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0063900

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.