Induction of apoptosis in MDA-MB-231 breast cancer cells by a PARP1-targeting PROTAC small molecule

2019 ◽  
Vol 55 (3) ◽  
pp. 369-372 ◽  
Author(s):  
Qiuye Zhao ◽  
Tianlong Lan ◽  
Shang Su ◽  
Yu Rao
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Small Molecule ◽  
Breast Cancer Cells ◽  
Induction Of Apoptosis ◽  
First Time

We report for the first time a PARP1-targeting PROTAC small molecule to selectively induce the cleavage of PARP1.

scholarly journals Breast Cancer Cell Re-Dissemination from Lung Metastases—A Mechanism for Enhancing Metastatic Burden

2021 ◽  
Vol 10 (11) ◽  
pp. 2340
Author(s):  
Lucia Borriello ◽  
John Condeelis ◽  
David Entenberg ◽  
Maja H. Oktay
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Metastatic Disease ◽  
Breast Cancer Cells ◽  
Lung Metastases ◽  
Primary Tumors ◽  
Metastatic Burden ◽  
First Time ◽  
Do So

Although metastatic disease is the primary cause of mortality in cancer patients, the mechanisms leading to overwhelming metastatic burden are still incompletely understood. Metastases are the endpoint of a series of multi-step events involving cancer cell intravasation, dissemination to distant organs, and outgrowth to metastatic colonies. Here we show, for the first-time, that breast cancer cells do not solely disseminate to distant organs from primary tumors and metastatic nodules in the lymph nodes, but also do so from lung metastases. Thus, our findings indicate that metastatic dissemination could continue even after the removal of the primary tumor. Provided that the re-disseminated cancer cells initiate growth upon arrival to distant sites, cancer cell re-dissemination from metastatic foci could be one of the crucial mechanisms leading to overt metastases and patient demise. Therefore, the development of new therapeutic strategies to block cancer cell re-dissemination would be crucial to improving survival of patients with metastatic disease.

scholarly journals Mutant p53L194F Harboring Luminal-A Breast Cancer Cells Are Refractory to Apoptosis and Cell Cycle Arrest in Response to MortaparibPlus, a Multimodal Small Molecule Inhibitor

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3043
Author(s):  
Ahmed Elwakeel ◽  
Anissa Nofita Sari ◽  
Jaspreet Kaur Dhanjal ◽  
Hazna Noor Meidinna ◽  
Durai Sundar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Small Molecule ◽  
Breast Cancer Cells ◽  
Luminal A ◽  
Molecular Analyses ◽  
Cycle Arrest ◽  
Mcf 7

We previously performed a drug screening to identify a potential inhibitor of mortalin–p53 interaction. In four rounds of screenings based on the shift in mortalin immunostaining pattern from perinuclear to pan-cytoplasmic and nuclear enrichment of p53, we had identified MortaparibPlus (4-[(1E)-2-(2-phenylindol-3-yl)-1-azavinyl]-1,2,4-triazole) as a novel synthetic small molecule. In order to validate its activity and mechanism of action, we recruited Luminal-A breast cancer cells, MCF-7 (p53wild type) and T47D (p53L194F) and performed extensive biochemical and immunocytochemical analyses. Molecular analyses revealed that MortaparibPlus is capable of abrogating mortalin–p53 interaction in both MCF-7 and T47D cells. Intriguingly, upregulation of transcriptional activation function of p53 (as marked by upregulation of the p53 effector gene—p21WAF1—responsible for cell cycle arrest and apoptosis) was recorded only in MortaparibPlus-treated MCF-7 cells. On the other hand, MortaparibPlus-treated T47D cells exhibited hyperactivation of PARP1 (accumulation of PAR polymer and decrease in ATP levels) as a possible non-p53 tumor suppression program. However, these cells did not show full signs of either apoptosis or PAR-Thanatos. Molecular analyses attributed such a response to the inability of MortaparibPlus to disrupt the AIF–mortalin complexes; hence, AIF did not translocate to the nucleus to induce chromatinolysis and DNA degradation. These data suggested that the cancer cells possessing enriched levels of such complexes may not respond to MortaparibPlus. Taken together, we report the multimodal anticancer potential of MortaparibPlus that warrants further attention in laboratory and clinical studies.

scholarly journals Roles of p53 and Caspases in Induction of Apoptosis in MCF-7 Breast Cancer Cells Treated with a Methanolic Extract of Nigella Sativa Seeds

2014 ◽  
Vol 15 (22) ◽  
pp. 9655-9660 ◽  
Author(s):  
Mohammed I. Alhazmi ◽  
Tarique N. Hasan ◽  
Gowhar Shafi ◽  
Abdullah H. Al-Assaf ◽  
Mohammed A. Alfawaz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Methanolic Extract ◽  
Nigella Sativa ◽  
Induction Of Apoptosis ◽  
Mcf 7

scholarly journals gef Gene Expression in MCF-7 Breast Cancer Cells is Associated with a Better Prognosis and Induction of Apoptosis by p53-Mediated Signaling Pathway

2011 ◽  
Vol 12 (11) ◽  
pp. 7445-7458 ◽  
Author(s):  
Houria Boulaiz ◽  
Pablo J. Álvarez ◽  
Jose Prados ◽  
Juan Marchal ◽  
Consolación Melguizo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Breast Cancer Cells ◽  
Induction Of Apoptosis ◽  
Mcf 7

scholarly journals Androstano-arylpyrimidines: Novel small molecule inhibitors of MDR1 for sensitizing multidrug-resistant breast cancer cells

2021 ◽  
Vol 156 ◽  
pp. 105587
Author(s):  
Mohana Krishna Gopisetty ◽  
Dóra Izabella Adamecz ◽  
Ferenc István Nagy ◽  
Ádám Baji ◽  
Vasiliki Lathira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Small Molecule ◽  
Breast Cancer Cells ◽  
Small Molecule Inhibitors ◽  
Multidrug Resistant
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