Therapeutic natural compounds Enzastaurin and Palbociclib inhibit MASTL kinase activity preventing breast cancer cell proliferation

Abstract

Microtubule-associated serine/threonine kinase-like (MASTL) regulates mitotic progression and is an attractive target for the development of new anticancer drugs. In this study, novel inhibitory molecules were screened against MASTL kinase, a protein involved in cell proliferation in breast cancer. Natural source-derived drugs Enzastaurin and Palbociclib were selected to identify their role as MASTL kinase inhibitors. Cytotoxic activity, kinase activity, and other cell-based assays of Enzastaurin and Palbociclib were evaluated on human breast cancer (MCF-7) cells. The potential natural compounds caused cytotoxicity in MCF-7 cells in a dose- and time-dependent manner. Further analysis by Annexin V and PI staining indicated that both drugs are potent inducers of apoptosis. Enzastaurin induced G2/M phase arrest, while Palbociclib caused G1 arrest. MASTL kinase activity was significantly abrogated with both the compounds showing EC 50 values of 17.13 µM and 10.51 µM, respectively. Taken together, these data strongly suggest that Enzastaurin and Palbociclib possess the ability to inhibit MASTL kinase activity and induce cell death in breast cancer cells, thus exhibiting significant therapeutic potential. Supplementary Information The online version contains supplementary material available at 10.1007/s12032-022-01701-3.

Proteomics of long-term neurodevelopmental disorders of rats exposed to early pain stimulation in the neonatal period

“…In addition, in the present results, early and repeated experiences of painful stimulation caused a signi cant upregulation of MASTL in adolescent hippocampal tissue and were involved in regulating chromosome condensation and cell division processes (19)(20)(21). MASTL is active in cell cycle progression and induces the mitotic transition by inhibiting the activity of the tumor suppressor PP2A-B55 phosphatase (22).…”

Novel indolyl 1,2,4-triazole derivatives as potential anti-proliferative agents: in silico studies, synthesis, and biological evaluation

“…The anticancer activities of the three FDA approved agents (palbociclib, ribociclib and abemaciclib) were also added for comparison and were obtained from the literature. [38][39][40][41] All data and results (IC 50 ) are summarized in Table 5. The results shown in Table 5 revealed that all compounds had promising cytotoxic activity against both MCF-7 and MDA-MB-231 cell lines with inhibitory activity ranging from 0.891 to 36.4 μM and 1.91 to 81.46 μM, respectively.…”

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“…The combined of CDK4/6 inhibitor Palbociclib and MEK inhibitor PD0325901 elicited a robust therapeutic response in KRAS-dependent and BRAF mutant colorectal cancer, both in vitro and in vivo. 50 Polisety et al 51 found that Enzastaurin and Palbociclib possessed the ability to induce cell death in breast cancer cells and exhibited significant synergistic therapeutic potential. Borre et al 52 found that combined PLX4720 and Dasatinib treatment induced apoptosis, increased immune cell infiltration, and reduced tumor volume in anaplastic thyroid cancer.…”