Mechanisms of cytotoxic activity of pyrrole-carboxamides against multidrug-resistant tumor cell sublines

Autor: A. R. Galembikova, P. D. Dunaev, F. F. Bikinieva, I. G. Mustafin, P. B. Kopnin, S. S. Zykova, F. I. Mukhutdinova, E. A. Sarbazyan, S. V. Boichuk
Jazyk: ruština
Rok vydání: 2023
Předmět:
Zdroj: Успехи молекулярной онкологии, Vol 10, Iss 3, Pp 59-71 (2023)
Druh dokumentu: article
ISSN: 2313-805X
2413-3787
DOI: 10.17650/2313-805X-2023-10-3-59-71
Popis: Introduction. Mitotic poisoning agents (MPAs) affecting the dynamic state of the microtubules, are the well-known and effective chemotherapeutic agents. Mitotic poisoning agents are binding to the microtubules, and thereby interfere with tubulin polymerization or depolymerization dynamic state, resulting in the cell cycle arrest in M-phase (mitotic catastrophe) and subsequent apoptotic cell death. We reported previously about potent cytotoxic activities against the pyrrole-carboxamides (PCs) (PC-61 and PC-84) against broad spectrum of cancer cell lines, including triple negative breast cancer, lung and prostate cancer.Aim. To examine the cytotoxic activities of PC-61 and PC-84 against multidrug-resistant cancer cell lines indicated above.Materials and methods. Studу was performed on the triple-negative paclitaxel-resistant breast cancer cell line HCC1806 Tx-R and doxorubicin-resistant osteosarcoma SaOS-2 Dox-R cell line.Results. The cytotoxic activity of PCs was due to the inhibition of tubulin polymerization. Immunofluorescence staining data revealed PC’s ability to interfere with tubulin’s assembly in multidrug-resistant cancer cell lines. As an outcome of inhibition of tubulin polymerization, PCs induced cell cycle arrest in M-phase, and further led to apoptotic cell death of cancer cells.Conclusion. Collectively, we demonstrated potent cytotoxic activity of PCs against cancer cell lines with multidrug-resistant phenotype, which arising the possibilities to develop novel and effective anti-tumor agents that belongs to mitotic poisoning agents
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