Molecular Diagnostic & Covid-19 Kit Testing Laboratory, National Institute of Biologicals (NIB), A-32, Sector-62, Institutional Area Noida, Noida, 201309, UP, India.
Department of Zoology, University of Lucknow, Lucknow, India.
Med Oncol. 2022 May 23;39(5):100. doi: 10.1007/s12032-022-01701-3.
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 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.
微管相关丝氨酸/苏氨酸激酶样（MASTL）调节有丝分裂进程，是开发新型抗癌药物的有吸引力的靶点。在这项研究中，针对参与乳腺癌细胞增殖的 MASTL 激酶筛选了新型抑制分子。选择天然来源药物恩杂鲁胺和帕博西利来确定它们作为 MASTL 激酶抑制剂的作用。在人乳腺癌（MCF-7）细胞上评估了恩杂鲁胺和帕博西利的细胞毒性、激酶活性和其他基于细胞的测定。潜在的天然化合物以剂量和时间依赖的方式在 MCF-7 细胞中引起细胞毒性。通过 Annexin V 和 PI 染色的进一步分析表明，这两种药物都能有效诱导细胞凋亡。恩杂鲁胺诱导 G2/M 期阻滞，而帕博西利则导致 G1 期阻滞。两种化合物均能显著抑制 MASTL 激酶活性，EC 值分别为 17.13µM 和 10.51µM。综上所述，这些数据强烈表明恩杂鲁胺和帕博西利具有抑制 MASTL 激酶活性和诱导乳腺癌细胞死亡的能力，从而表现出显著的治疗潜力。
