A novel benzothiazole derivative YLT322 induces apoptosis via the mitochondrial apoptosis pathway in vitro with anti-tumor activity in solid malignancies
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....
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Published in | PloS one Vol. 8; no. 5; p. e63900 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
30.05.2013
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | Conceived and designed the experiments: YLT SXJ XY. Performed the experiments: SXJ XY YTH. Analyzed the data: YLT SXJ WNY ZYX. Contributed reagents/materials/analysis tools: XYZ ZLD SXH SYJ. Wrote the paper: SXJ XY WNY. Competing Interests: This work was supported by Shijiazhuang Pharmaceutical Group Co., Ltd. (project name SKLB163; contract number 11H0684). There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0063900 |