Investigating the anticancer properties of six benzothiazolopyrimidine derivatives on colon carcinoma cells, in vitro and in vivo.

Autor: Bakharzi M; Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.; Department of Interdisciplinary Oncology, Faculty of Medicine, University of British Columbia, Vancouver, Canada., Attar E; Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran., Garmabi H; Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran., Esmaeili AA; Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran., Bahrami AR; Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.; Industrial Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran., Danehchin M; Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran., Matin MM; Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.; Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.
Jazyk: angličtina
Zdroj: Journal of biochemical and molecular toxicology [J Biochem Mol Toxicol] 2024 Aug; Vol. 38 (8), pp. e23779.
DOI: 10.1002/jbt.23779
Abstrakt: Colorectal cancer (CRC) is the third most common cancer in the world. Despite considerable improvements in the treatment of this cancer, further research to discover novel and more effective agents is ongoing. In this study, possible cytotoxic and apoptotic properties of six benzothiazolopyrimidine derivatives were studied. To assess the IC 50 values of these agents, MTT assay was performed on HCT 116, CT26, and NIH/3T3 cells. Moreover, cell death mechanism induced by studied compounds was evaluated by PI/annexin V staining. Then, based on molecular docking results and in vitro experiments, the compounds with the highest anticancer properties were further analyzed in vivo in a mouse model of CRC. MTT results indicated that BTP(1) and BTP(4) had the highest selective cytotoxicity on colorectal cancer cells. Furthermore, flow cytometry results demonstrated a considerable increase in the percentage of the early apoptotic cells in BTP(1)- and BTP(4)-treated groups. In vivo studies confirmed the antitumor properties of the two compounds by a significant regression in tumor size of BTP(1)- and BTP(4)-treated mice compared to control groups. Histopathological examination of tumor tissues showed an increased number of apoptotic cells in these two groups compared to the control animals. Additionally, hematoxylin and eosin staining of the spleen and liver of treated mice did not exhibit considerable tissue damage. Thus, BTP(1) and BTP(4) can be considered promising agents in the treatment of colorectal cancer, although further experiments are required to assess their mechanism of action before their application in clinical studies.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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