Investigating the anticancer properties of six benzothiazolopyrimidine derivatives on colon carcinoma cells, in vitro and in vivo.
Melika BakharziElham AttarHossein GarmabiAbbas Ali EsmaeiliAhmad Reza BahramiMaryam DanehchinMaryam M MatinPublished in: Journal of biochemical and molecular toxicology (2024)
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.
Keyphrases
- cell death
- cell cycle arrest
- flow cytometry
- molecular docking
- induced apoptosis
- mouse model
- oxidative stress
- gene expression
- computed tomography
- molecular dynamics simulations
- anti inflammatory
- squamous cell carcinoma
- newly diagnosed
- cell proliferation
- adipose tissue
- positron emission tomography
- replacement therapy
- structure activity relationship