“…Studies investigated MASTL to be an important drug target for anticancer treatment due to its multifarious roles, such as cellular transformation, metastasis, chromosomal instability, and the DNA damage response in various cancers [ 10 , 11 , 25 ]. MASTL is an important therapeutic drug target in breast cancer.…”
Section: Discussionmentioning
confidence: 99%
“…These findings suggest that MASTL is a new breast cancer oncogene that may overcome contact inhibition, invasion, and chromosomal instability [ 10 ]. Overall, the evidence revealed that MASTL can be a promising target for selective anticancer treatment [ 11 ]. Fig.…”
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.
“…Studies investigated MASTL to be an important drug target for anticancer treatment due to its multifarious roles, such as cellular transformation, metastasis, chromosomal instability, and the DNA damage response in various cancers [ 10 , 11 , 25 ]. MASTL is an important therapeutic drug target in breast cancer.…”
Section: Discussionmentioning
confidence: 99%
“…These findings suggest that MASTL is a new breast cancer oncogene that may overcome contact inhibition, invasion, and chromosomal instability [ 10 ]. Overall, the evidence revealed that MASTL can be a promising target for selective anticancer treatment [ 11 ]. Fig.…”
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.
“…Studies investigated MASTL to be an important drug target for anticancer treatment due to its multifarious roles such as cellular transformation, metastasis, chromosomal instability, and the DNA damage response in various cancers [10,11,24]. MASTL is reported to be upregulated in several cancer cell lines including breast cancer cells [4,[25][26][27].…”
Section: Discussionmentioning
confidence: 99%
“…These ndings suggest that MASTL is a new breast cancer oncogene that may overcome contact inhibition, invasion, and chromosomal instability [10]. Overall, the evidence revealed that MASTL can be a promising target for selective anticancer treatment [11].…”
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 EC50 values of 17.13µM and 10.51µM 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.
“…More recently, its roles have expanded to include meiosis 8-10 , recovery from DNA damage [11][12][13] , DNA replication 14 , platelet maturation 15,16 , cell migration and actomyosin contraction 17 . Unsurprisingly, these roles have led to MASTL being identi ed as a potential oncogenic kinase 18 with upregulation and over-expression correlating with poor patient outcomes in a variety of cancer types, including breast [19][20][21] , colon 22,23 uterine 22 , head and neck 24 and pancreatic cancer 25 . Conversely, knockdown of MASTL has also been shown to sensitize cancer cells to a variety of DNA damaging therapies including radiotherapy 26 , cisplatin 24,27 and gemcitabine 25 .…”
MASTL (microtubule-associated serine/threonine kinase-like) has emerged as a critical regulator of mitosis and as a potential oncogene in a variety of cancer types. To date, Arpp-19/ENSA are the only known substrates of MASTL. However, with the roles of MASTL expanding and increased interest in development of MASTL inhibitors, it has become critical to determine if there are additional substrates and what the optimal consensus motif for MASTL is. Here we utilized a whole cell lysate (in cellulo) kinase screen approach combined with stable isotope labelling of amino acids in cell culture to identify potential substrates and a consensus motif of MASTL. Using the related AGC kinase family members AKT1/2, the in cellulo assay identified several known and new substrates highly enriched with the validated consensus motif for AKT. Applying this method to MASTL identified 59 phospho-sites on 26 novel proteins significantly increased in the presence of active MASTL. Subsequent in vitro kinase assays confirmed that MASTL was capable of phosphorylating hnRNPM, YB1, RPS6, TUBA1C, and RPL36A under some conditions. Taken together, these data suggest that MASTL may phosphorylate several additional substrates, providing insight into the ever-increasing biological functions and roles MASTL plays in driving cancer progression and therapy resistance.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
