scholarly journals Inhibition of Cyclin-Dependent Kinase Activity and Induction of Apoptosis by Preussin in Human Tumor Cells

2000 ◽  
Vol 44 (10) ◽  
pp. 2794-2801 ◽  
Author(s):  
Tatjana V. Achenbach ◽  
Emily P. Slater ◽  
Harm Brummerhop ◽  
Thorsten Bach ◽  
Rolf Müller
Keyword(s):  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
Human Cancer ◽  
Cyclin E ◽  
Human Tumor ◽  
Chemotherapeutic Agents ◽  
Cyclin Dependent Kinase ◽  
Human Cancer Cells ◽  
Induction Of Apoptosis

ABSTRACT In this paper, we report that (+)-preussin, a pyrrolidinol alkaloid originally identified as an antifungal agent, has growth-inhibitory and cytotoxic effects on human cancer cells. Preussin was found to be a potent inhibitor of cyclin E kinase (CDK2-cyclin E) in vitro (50% inhibitory concentration; ∼500 nM) and to inhibit cell cycle progression into S phase. In agreement with these findings, the level of the cyclin-dependent kinase inhibitor p27KIP-1 is increased in response to preussin treatment while the expression of both cyclin A and the transcription factor E2F-1 is down-regulated. Preussin also induces programmed cell death (apoptosis), which requires caspase activation and involves the release of cytochrome cfrom mitochondria. This induction of apoptosis is not blocked by high levels of Bcl-2, which usually confers resistance to chemotherapeutic agents. Taken together, our data indicate that preussin could be a promising lead compound for the development of a new class of potent antitumor drugs.

scholarly journals Induction of apoptosis by in vitro and in vivo plant extracts derived from Menyanthes trifoliata L. in human cancer cells

2019 ◽  
Vol 71 (1) ◽  
pp. 165-180 ◽  
Author(s):  
Tomasz Kowalczyk ◽  
Przemysław Sitarek ◽  
Ewa Skała ◽  
Monika Toma ◽  
Marzena Wielanek ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Plant Extracts ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
Induction Of Apoptosis ◽  
Menyanthes Trifoliata

Antioxidant and In Vitro Anticancer Effect of 2-Pyrrolidinone Rich Fraction of Brassica oleracea var. capitata Through Induction of Apoptosis in Human Cancer Cells

2013 ◽  
Vol 27 (11) ◽  
pp. 1664-1670 ◽  
Author(s):  
Ramar Thangam ◽  
Veeraperumal Suresh ◽  
Mayan Rajkumar ◽  
Jally Damien Vincent ◽  
Palani Gunasekaran ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Brassica Oleracea ◽  
Human Cancer ◽  
Anticancer Effect ◽  
Human Cancer Cells ◽  
Induction Of Apoptosis

scholarly journals Solutions for the Cell Cycle in Cell Lines Derived from Human Tumors

2006 ◽  
Vol 7 (4) ◽  
pp. 215-228 ◽  
Author(s):  
B. Zubik-Kowal
Keyword(s):  
Human Cancer ◽  
Human Tumor ◽  
Number Density ◽  
Human Tumor Cells ◽  
Human Cancer Cells ◽  
Relative Dna Content ◽  
Model Equations ◽  
The Mathematical Model ◽  
Kinetics Of

The goal of the paper is to compute efficiently solutions for model equations that have the potential to describe the growth of human tumor cells and their responses to radiotherapy or chemotherapy. The mathematical model involves four unknown functions of two independent variables: the time variabletand dimensionless relative DNA contentx. The unknown functions can be thought of as the number density of cells and are solutions of a system of four partial differential equations. We construct solutions of the system, which allow us to observe the number density of cells for differenttandxvalues. We present results of our experiments which simulate population kinetics of human cancer cellsin vitro. Our results show a correspondence between predicted and experimental data.

Structure-Reactivity Relationships on Substrates and Inhibitors of the Lysine Deacylase Sirtuin 2 from Schistosoma Mansoni (SmSirt2)

2019 ◽  
Author(s):  
Daria Monaldi ◽  
Dante Rotili ◽  
Julien Lancelot ◽  
Martin Marek ◽  
Nathalie Wössner ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Human Cancer ◽  
Egg Laying ◽  
Human Cancer Cells ◽  
Parasite Survival ◽  
Survival And Reproduction ◽  
Emergence Of Resistance ◽  
First Time ◽  
Parasitic Life Cycle

The only drug for treatment of Schistosomiasis is Praziquantel, and the possible emergence of resistance makes research on novel therapeutic agents necessary. Targeting of Schistosoma mansoni epigenetic enzymes, which regulate the parasitic life cycle, emerged as promising approach. Due to the strong effects of human Sirtuin inhibitors on parasite survival and reproduction, Schistosoma sirtuins were postulated as therapeutic targets. In vitro testing of synthetic substrates of S. mansoni Sirtuin 2 (SmSirt2) and kinetic experiments on a myristoylated peptide demonstrated lysine long chain deacylation as an intrinsic SmSirt2 activity for the first time. Focused in vitro screening of the GSK Kinetobox library and structure-activity relationships (SAR) of identified hits, led to the first SmSirt2 inhibitors with activity in the low micromolar range. Several SmSirt2 inhibitors showed potency against both larval schistosomes (viability) and adult worms (pairing, egg laying) in culture without general toxicity to human cancer cells.<br>

scholarly journals A New Smoothened Antagonist Bearing the Purine Scaffold Shows Antitumour Activity In Vitro and In Vivo

2021 ◽  
Vol 22 (16) ◽  
pp. 8372
Author(s):  
Ana María Zárate ◽  
Christian Espinosa-Bustos ◽  
Simón Guerrero ◽  
Angélica Fierro ◽  
Felipe Oyarzún-Ampuero ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Antitumour Activity ◽  
Anticancer Compounds ◽  
Human Cancer Cells ◽  
Cycle Arrest ◽  
Apoptosis Inducer ◽  
Purine Ring

The Smoothened (SMO) receptor is the most druggable target in the Hedgehog (HH) pathway for anticancer compounds. However, SMO antagonists such as vismodegib rapidly develop drug resistance. In this study, new SMO antagonists having the versatile purine ring as a scaffold were designed, synthesised, and biologically tested to provide an insight to their mechanism of action. Compound 4s was the most active and the best inhibitor of cell growth and selectively cytotoxic to cancer cells. 4s induced cell cycle arrest, apoptosis, a reduction in colony formation and downregulation of PTCH and GLI1 expression. BODIPY-cyclopamine displacement assays confirmed 4s is a SMO antagonist. In vivo, 4s strongly inhibited tumour relapse and metastasis of melanoma cells in mice. In vitro, 4s was more efficient than vismodegib to induce apoptosis in human cancer cells and that might be attributed to its dual ability to function as a SMO antagonist and apoptosis inducer.

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