scholarly journals Discovery and Characterization of a Novel MASTL Inhibitor MKI-2 Targeting MASTL-PP2A in Breast Cancer Cells and Oocytes

2021 ◽  
Vol 14 (7) ◽  
pp. 647
Author(s):  
Minsung Kang ◽  
Chijung Kim ◽  
Jiyeon Leem ◽  
Ye-hyun Kim ◽  
Young-ju Kwon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Kinase Inhibitor ◽  
Mitotic Catastrophe ◽  
Serine Threonine Kinase ◽  
Promising Target ◽  
Drug Discovery Program ◽  
Ic50 Values ◽  
Anticancer Treatment

Although microtubule-associated serine/threonine kinase-like (MASTL) is a promising target for selective anticancer treatment, MASTL inhibitors with nano range potency and antitumor efficacy have not been reported. Here, we report a novel potent and selective MASTL inhibitor MASTL kinase inhibitor-2 (MKI-2) identified in silico through a drug discovery program. Our data showed that MKI-2 inhibited recombinant MASTL activity and cellular MASTL activity with IC50 values of 37.44 nM and 142.7 nM, respectively, in breast cancer cells. In addition, MKI-2 inhibited MASTL kinase rather than other AGC kinases, such as ROCK1, AKT1, PKACα, and p70S6K. Furthermore, MKI-2 exerted various antitumor activities by inducing mitotic catastrophe resulting from the modulation of the MASTL-PP2A axis in breast cancer cells. The MKI-2 treatment showed phenocopies with MASTL-null oocyte in mouse oocytes, which were used as a model to validate MKI-2 activity. Therefore, our study provided a new potent and selective MASTL inhibitor MKI-2 targeting the oncogenic MAST-PP2A axis in breast cancer cells.

scholarly journals Synthesis and Biological Evaluation of 1-(Diarylmethyl)-1H-1,2,4-triazoles and 1-(Diarylmethyl)-1H-imidazoles as a Novel Class of Anti-Mitotic Agent for Activity in Breast Cancer

2021 ◽  
Vol 14 (2) ◽  
pp. 169
Author(s):  
Gloria Ana ◽  
Patrick M. Kelly ◽  
Azizah M. Malebari ◽  
Sara Noorani ◽  
Seema M. Nathwani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Mitotic Catastrophe ◽  
Phase Cell ◽  
Computational Docking ◽  
Er Positive ◽  
Mcf 7

We report the synthesis and biochemical evaluation of compounds that are designed as hybrids of the microtubule targeting benzophenone phenstatin and the aromatase inhibitor letrozole. A preliminary screening in estrogen receptor (ER)-positive MCF-7 breast cancer cells identified 5-((2H-1,2,3-triazol-1-yl)(3,4,5-trimethoxyphenyl)methyl)-2-methoxyphenol 24 as a potent antiproliferative compound with an IC50 value of 52 nM in MCF-7 breast cancer cells (ER+/PR+) and 74 nM in triple-negative MDA-MB-231 breast cancer cells. The compounds demonstrated significant G2/M phase cell cycle arrest and induction of apoptosis in the MCF-7 cell line, inhibited tubulin polymerisation, and were selective for cancer cells when evaluated in non-tumorigenic MCF-10A breast cells. The immunofluorescence staining of MCF-7 cells confirmed that the compounds targeted tubulin and induced multinucleation, which is a recognised sign of mitotic catastrophe. Computational docking studies of compounds 19e, 21l, and 24 in the colchicine binding site of tubulin indicated potential binding conformations for the compounds. Compounds 19e and 21l were also shown to selectively inhibit aromatase. These compounds are promising candidates for development as antiproliferative, aromatase inhibitory, and microtubule-disrupting agents for breast cancer.

scholarly journals Estrogen-mediated epigenetic repression of the imprinted gene cyclin-dependent kinase inhibitor 1C in breast cancer cells

2011 ◽  
Vol 32 (6) ◽  
pp. 812-821 ◽  
Author(s):  
Benjamin A.T. Rodriguez ◽  
Yu-I Weng ◽  
Ta-Ming Liu ◽  
Tao Zuo ◽  
Pei-Yin Hsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Kinase Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Imprinted Gene ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Epigenetic Repression

RPF101, a new capsaicin-like analogue, disrupts the microtubule network accompanied by arrest in the G2/M phase, inducing apoptosis and mitotic catastrophe in the MCF-7 breast cancer cells

2013 ◽  
Vol 266 (3) ◽  
pp. 385-398 ◽  
Author(s):  
Paulo Luiz de-Sá-Júnior ◽  
Kerly Fernanda Mesquita Pasqualoto ◽  
Adilson Kleber Ferreira ◽  
Maurício Temotheo Tavares ◽  
Mariana Celestina Frojuello Damião ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mitotic Catastrophe ◽  
Microtubule Network ◽  
M Phase ◽  
Mcf 7

scholarly journals Cytotoxic, Anti-Migration, and Anti-Invasion Activities on Breast Cancer Cells of Angucycline Glycosides Isolated from a Marine-Derived Streptomyces sp.

Marine Drugs ◽  
2019 ◽  
Vol 17 (5) ◽  
pp. 277 ◽  
Author(s):  
Xin-Ying Qu ◽  
Jin-Wei Ren ◽  
Ai-Hong Peng ◽  
Shi-Qi Lin ◽  
Dan-Dan Lu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Ring Cleavage ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Streptomyces Sp ◽  
Deoxy Sugar ◽  
Ic50 Values ◽  
Dose Dependent

Four angucycline glycosides were previously characterized from marine-derived Streptomyces sp. OC1610.4. Further investigation of this strain cultured on different fermentation media from that used previously resulted in the isolation of two new angucycline glycosides, vineomycins E and F (1–2), and five known homologues, grincamycin L (3), vineomycinone B2 (4), fridamycin D (5), moromycin B (7), and saquayamycin B1 (8). Vineomycin F (2) contains an unusual ring-cleavage deoxy sugar. All the angucycline glycosides isolated from Streptomyces sp. OC1610.4 were evaluated for their cytotoxic activity against breast cancer cells MCF-7, MDA-MB-231, and BT-474. Moromycin B (7), saquayamycin B1 (8), and saquayamycin B (9) displayed potent anti-proliferation against the tested cell lines, with IC50 values ranging from 0.16 to 0.67 μM. Saquayamycin B (9) inhibited the migration and invasion of MDA-MB-231 cells in a dose-dependent manner, as detected by Transwell and wound-healing assays.

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