PUBLICATION
Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer
- Authors
- Hermanowicz, J.M., Szymanowska, A., Sieklucka, B., Czarnomysy, R., Pawlak, K., Bielawska, A., Bielawski, K., Kalafut, J., Przybyszewska, A., Surazynski, A., Rivero-Muller, A., Mojzych, M., Pawlak, D.
- ID
- ZDB-PUB-210202-18
- Date
- 2021
- Source
- Journal of enzyme inhibition and medicinal chemistry 36: 535-548 (Journal)
- Registered Authors
- Keywords
- 1,2,4-Triazine derivative, apoptosis, colon cancer, zebrafish
- MeSH Terms
-
- Animals
- Antineoplastic Agents/chemical synthesis
- Antineoplastic Agents/chemistry
- Antineoplastic Agents/pharmacology*
- Cell Proliferation/drug effects
- Cell Survival/drug effects
- Colorectal Neoplasms/drug therapy*
- Colorectal Neoplasms/metabolism
- Colorectal Neoplasms/pathology
- Dose-Response Relationship, Drug
- Drug Screening Assays, Antitumor
- Humans
- Molecular Structure
- Neoplasms, Experimental/drug therapy
- Neoplasms, Experimental/metabolism
- Neoplasms, Experimental/pathology
- Structure-Activity Relationship
- Triazines/chemical synthesis
- Triazines/chemistry
- Triazines/pharmacology*
- Tumor Cells, Cultured
- Zebrafish
- PubMed
- 33522320 Full text @ J Enzyme Inhib Med Chem
Citation
Hermanowicz, J.M., Szymanowska, A., Sieklucka, B., Czarnomysy, R., Pawlak, K., Bielawska, A., Bielawski, K., Kalafut, J., Przybyszewska, A., Surazynski, A., Rivero-Muller, A., Mojzych, M., Pawlak, D. (2021) Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer. Journal of enzyme inhibition and medicinal chemistry. 36:535-548.
Abstract
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in men and in women. The impact of the new pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulphonamide (MM-129) was evaluated against human colon cancer in vitro and in zebrafish xenografts. Our results show that this new synthesised compound effectively inhibits cell survival in BTK-dependent mechanism. Its effectiveness is much higher at a relatively low concentration as compared with the standard chemotherapy used for CRC, i.e. 5-fluorouracil (5-FU). Flow cytometry analysis after annexin V-FITC and propidium iodide staining revealed that apoptosis was the main response of CRC cells to MM-129 treatment. We also found that MM-129 effectively inhibits tumour development in zebrafish embryo xenograft model, where it showed a markedly synergistic anticancer effect when used in combination with 5-FU. The above results suggest that this novel heterofused 1,2,4-triazine derivative may be a promising candidate for further evaluation as chemotherapeutic agent against CRC.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping