scholarly journals Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53

2005 ◽  
Vol 168 (4) ◽  
pp. 553-560 ◽  
Author(s):  
Kayoko Maehara ◽  
Kimi Yamakoshi ◽  
Naoko Ohtani ◽  
Yoshiaki Kubo ◽  
Akiko Takahashi ◽  
...  

E2F/DP complexes were originally identified as potent transcriptional activators required for cell proliferation. However, recent studies revised this notion by showing that inactivation of total E2F/DP activity by dominant-negative forms of E2F or DP does not prevent cellular proliferation, but rather abolishes tumor suppression pathways, such as cellular senescence. These observations suggest that blockage of total E2F/DP activity may increase the risk of cancer. Here, we provide evidence that depletion of DP by RNA interference, but not overexpression of dominant-negative form of E2F, efficiently reduces endogenous E2F/DP activity in human primary cells. Reduction of total E2F/DP activity results in a dramatic decrease in expression of many E2F target genes and causes a senescence-like cell cycle arrest. Importantly, similar results were observed in human cancer cells lacking functional p53 and pRB family proteins. These findings reveal that E2F/DP activity is indeed essential for cell proliferation and its reduction immediately provokes a senescence-like cell cycle arrest.

2021 ◽  
Vol 19 (1) ◽  
pp. 119-127
Author(s):  
Ibrahim O. Barnawi ◽  
Fahd A. Nasr ◽  
Omar M. Noman ◽  
Ali S. Alqahtani ◽  
Mohammed Al-zharani ◽  
...  

Abstract Different phytochemicals from various plant species exhibit promising medicinal properties against cancer. Juniperus phoenicea is a plant species that has been found to present medicinal properties. Herein, crude extract and fractions of J. phoenicea were examined to determine its anticancer properties against several cancer cells. The active fraction was chosen to assess its activity on cell cycle progression and apoptosis induction by annexin and propidium iodide (PI) biomarkers. Further, phytochemical screening for possible contents of active fraction using gas chromatography–mass spectrometry (GC-MS) analysis was conducted. It was demonstrated that cell proliferation was suppressed, and the MCF-7 cell line was the most sensitive to J. phoenicea chloroform fraction (JPCF), with the IC50 values of 24.5 μg/mL. The anti-proliferation activity of JPCF in MCF-7 cells was linked to the aggregation of cells in the G1 phase, increases in early and late apoptosis as well as necrotic cell death. Contents analysis of JPCF using GC-MS analysis identified 3-methyl-5-(2′,6′,6′-trimethylcyclohex-1′-enyl)-1-penten-3-ol (16.5%), methyl 8-oxooctanoate (15.61%), cubenol (13.48%), and 7-oxabicyclo [2.2.1] heptane (12.14%) as major constituents. Our present study provides clear evidence that J. phoenicea can inhibit cell proliferation, trigger cell cycle arrest, and induce apoptosis in tested cancer cells.


Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 451 ◽  
Author(s):  
Sergey A. Dyshlovoy ◽  
Darya Tarbeeva ◽  
Sergey Fedoreyev ◽  
Tobias Busenbender ◽  
Moritz Kaune ◽  
...  

From a root bark of Lespedeza bicolor Turch we isolated two new (7 and 8) and six previously known compounds (1–6) belonging to the group of prenylated polyphenols. Their structures were elucidated using mass spectrometry, nuclear magnetic resonance and circular dichroism spectroscopy. These natural compounds selectively inhibited human drug-resistant prostate cancer in vitro. Prenylated pterocarpans 1–3 prevented the cell cycle progression of human cancer cells in S-phase. This was accompanied by a reduced expression of mRNA corresponding to several human cyclin-dependent kinases (CDKs). In contrast, compounds 4–8 induced a G1-phase cell cycle arrest without any pronounced effect on CDKs mRNA expression. Interestingly, a non-substituted hydroxy group at C-8 of ring D of the pterocarpan skeleton of compounds 1–3 seems to be important for the CDKs inhibitory activity.


2011 ◽  
Vol 10 (2) ◽  
pp. 269-278 ◽  
Author(s):  
Keqiang Zhang ◽  
Jun Wu ◽  
Xiwei Wu ◽  
Xiaochen Wang ◽  
Yan Wang ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document