Novel small molecule inhibitor of Kpnβ1 induces cell cycle arrest and apoptosis in cancer cells

2021 ◽  
pp. 112637
Author(s):  
Aderonke Ajayi-Smith ◽  
Pauline van der Watt ◽  
Nonkululeko Mkwanazi ◽  
Sarah Carden ◽  
John O. Trent ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Cycle Arrest ◽  
Molecule Inhibitor ◽  
Apoptosis In Cancer Cells

Induction of cell-cycle arrest and apoptosis in glioblastoma stem-like cells by WP1193, a novel small molecule inhibitor of the JAK2/STAT3 pathway

2012 ◽  
Vol 107 (3) ◽  
pp. 487-501 ◽  
Author(s):  
Ke Sai ◽  
Shuzhen Wang ◽  
Veerakumar Balasubramaniyan ◽  
Charles Conrad ◽  
Frederick F. Lang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Stat3 Pathway ◽  
Cycle Arrest ◽  
Molecule Inhibitor

scholarly journals PFK15, a Small Molecule Inhibitor of PFKFB3, Induces Cell Cycle Arrest, Apoptosis and Inhibits Invasion in Gastric Cancer

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0163768 ◽  
Author(s):  
Wei Zhu ◽  
Liang Ye ◽  
Jianzhao Zhang ◽  
Pengfei Yu ◽  
Hongbo Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Cycle Arrest ◽  
Molecule Inhibitor

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 N-Myristoyltransferase Inhibition Induces ER-Stress, Cell Cycle Arrest, and Apoptosis in Cancer Cells

2016 ◽  
Vol 11 (8) ◽  
pp. 2165-2176 ◽  
Author(s):  
Emmanuelle Thinon ◽  
Julia Morales-Sanfrutos ◽  
David J. Mann ◽  
Edward W. Tate
Keyword(s):  
Cell Cycle ◽  
Er Stress ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Cycle Arrest ◽  
Apoptosis In Cancer Cells

Critical Role of AMPK/FoxO3A Axis in Globular Adiponectin-Induced Cell Cycle Arrest and Apoptosis in Cancer Cells

2015 ◽  
Vol 231 (2) ◽  
pp. 357-369 ◽  
Author(s):  
Anup Shrestha ◽  
Saroj Nepal ◽  
Mi Jin Kim ◽  
Jae Hoon Chang ◽  
Sang-Hyun Kim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Critical Role ◽  
Cycle Arrest ◽  
Globular Adiponectin ◽  
Apoptosis In Cancer Cells

Gephyromycin C, a novel small-molecule inhibitor of heat shock protein Hsp90, induces G2/M cell cycle arrest and apoptosis in PC3 cells in vitro

2020 ◽  
Vol 531 (3) ◽  
pp. 377-382
Author(s):  
Wan-jing Ding ◽  
Yuan-yuan Ji ◽  
Yong-jun Jiang ◽  
Wei-jia Ying ◽  
Zhang-yun Fang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Cycle Arrest ◽  
Small Molecule ◽  
M Cell ◽  
Cycle Arrest ◽  
Molecule Inhibitor ◽  
Pc3 Cells

scholarly journals Piper nigrum ethanolic extract rich in piperamides causes ROS overproduction, oxidative damage in DNA leading to cell cycle arrest and apoptosis in cancer cells

2016 ◽  
Vol 189 ◽  
pp. 139-147 ◽  
Author(s):  
Valdelúcia Maria Alves de Souza Grinevicius ◽  
Maicon Roberto Kviecinski ◽  
Nádia Sandrini Ramos Santos Mota ◽  
Fabiana Ourique ◽  
Luiza Sheyla Evenni Porfirio Will Castro ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Oxidative Damage ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Ethanolic Extract ◽  
Piper Nigrum ◽  
Cycle Arrest ◽  
Apoptosis In Cancer Cells

Effect of a small-molecule MDM2/MDMX inhibitor on cell cycle arrest and apoptosis in breast cancer cells.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22096-e22096
Author(s):  
Qian Qian Geng ◽  
En Xiao Li ◽  
Dan Feng Dong ◽  
Yin Ying Wu ◽  
Jie Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Growth ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Small Molecule ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
Cycle Arrest ◽  
Mdm2 Inhibitor

e22096 Background: The MDM2 inhibitor which disrupted the MDM2-p53 interaction made little effort on the activation of p53 for breast cancer treatments, due to MDMX over expression. Previously a small molecule inhibitor targeting at MDM2 and MDMX had been successfully synthesized. We tested anti-tumor activity of the small molecule MDM2/MDMX inhibitor, compared with nutlin-3α, a well characterized MDM2 inhibitor, in the wild-type (wt) and mutant (mt) p53 breast cancer cell lines. Methods: Human breast cancer cell lines MCF-7 (wt-p53), ZR-7530 (wt-p53), BT-474 (mt-p53) and MDA-MB-231 (mt-p53) were cultured and treated with the small molecule MDM2/MDMX inhibitor, nutlin-3α or phosphate buffer solution (PBS) for 48 hrs separately. MTT for cell viability, FCM for cell cycle arrest and Annexin V FITC/PI for cell apoptosis were performed. The mechanism of antitumor activity of the small molecule MDM2/MDMX inhibitor was determined by Western-Blot analysis. Results: The inhibitor of MDM2 and MDMX inhibited cell growth and induced cell cycle arrest and apoptosis in mt-p53 breast cancer cells while nutlin-3α cannot. In the breast cancer cells with wt-p53, both of them inhibited cell growth, induced cell cycle arrest and apoptosis, but MDM2/MDMX inhibitor was proven to be more effective. Western Blot revealed that there was higher level of p53 expression in breast cancer cells treated with MDM2/MDMX inhibitor than nutlin-3α. The marked increases in p21, Bax and PUMA expressions were abserved in both wt-p53 and mt-p53 breast cancer cells which indicated that the small molecule MDM2/MDMX inhibitor induced cell apoptosis through p21, Bax and PUMA over expressions. Conclusions: The small molecule MDM2/MDMX inhibitor would be able to suppress cell proliferation, induce cell cycle arrest and apoptosis, activate p53 more effective than nutlin-3α in breast cancer cells, no matter with p53 status. P21, Bax and PUMA were involved in the mechanism of apoptosis induction. The inhibitor of targeting at both MDM2 and MDMX will be a novel treatment for breast cancer p53-independent status in the future.

Sign in / Sign up

Export Citation Format

Share Document