scholarly journals Enzymatic and Biological Characterization of Novel Sirtuin Modulators against Cancer

2019 ◽  
Vol 20 (22) ◽  
pp. 5654 ◽  
Author(s):  
Vincenzo Carafa ◽  
Angelita Poziello ◽  
Laura Della Torre ◽  
Pia Giovannelli ◽  
Marzia Di Donato ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Cycle Progression ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Cellular Level ◽  
Human Cancer Cell Lines ◽  
Regulation Of Cell Cycle

Sirtuins, a family of nicotinamide adenine dinucleotide (NAD+)-dependent lysine deacetylases, are promising targets for anticancer treatment. Recently, we characterized a novel pan-sirtuin (SIRT) inhibitor, MC2494, displaying antiproliferative effects and able to induce death pathways in several human cancer cell lines and decrease tumor growth in vivo. Based on the chemical scaffold of MC2494, and by applying a structure–activity relationship approach, we developed a small library of derivative compounds and extensively analyzed their enzymatic action at cellular level as well as their ability to induce cell death. We also investigated the effect of MC2494 on regulation of cell cycle progression in different cancer cell lines. Our investigations indicated that chemical substitutions applied to MC2494 scaffold did not confer higher efficacy in terms of biological activity and SIRT1 inhibition, but carbethoxy-containing derivatives showed higher SIRT2 specificity. The carbethoxy derivative of MC2494 and its 2-methyl analog displayed the strongest enzymatic activity. Applied chemical modifications improved the enzymatic selectivity of these SIRT inhibitors. Additionally, the observed activity of MC2494 via cell cycle and apoptotic regulation and inhibition of cell migration supports the potential role of SIRTs as targets in tumorigenesis and makes SIRT-targeting molecules good candidates for novel pharmacological approaches in personalized medicine.

scholarly journals Effect of lycopene on cell viability and cell cycle progression in human cancer cell lines

2012 ◽  
Vol 12 (1) ◽  
pp. 36 ◽  
Author(s):  
Anderson Teodoro ◽  
Felipe Oliveira ◽  
Nathalia Martins ◽  
Guilherme de Maia ◽  
Renata Martucci ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Cycle Progression ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Cycle Progression ◽  
Human Cancer Cell Lines

Oleiferasaponin C6 from the seeds of Camellia oleifera Abel.: a novel compound inhibits proliferation through inducing cell-cycle arrest and apoptosis on human cancer cell lines in vitro

RSC Advances ◽  
2016 ◽  
Vol 6 (94) ◽  
pp. 91386-91393 ◽  
Author(s):  
Jianfa Zong ◽  
Dongxu Wang ◽  
Weiting Jiao ◽  
Liang Zhang ◽  
Guanhu Bao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Camellia Oleifera ◽  
Human Cancer Cell Lines ◽  
Cycle Arrest

Oleiferasaponin C6 was isolated from Camellia oleifera Abel. and inhibits proliferation through inducing cell-cycle arrest and apoptosis on cancer cell lines in vitro.

Synthesis, Antiproliferative activity, and apoptotic profile of New Derivatives from the Meta Stable Benzoxazinone Scaffold

2021 ◽  
Vol 21 ◽  
Author(s):  
Amira El-Sayed ◽  
Maher El-Hashash ◽  
Wael El-Sayed
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Antiproliferative Activity ◽  
Human Cancer ◽  
Human Fibroblasts ◽  
Cancer Cell Lines ◽  
Selectivity Index ◽  
Human Cancer Cell Lines

Background: Cancer exerts a huge strain on the health system. The emerging resistance to the current chemotherapies demands the continuous development of new anticancer agents with lower cost, higher efficacy, and greater specificity. Objective: Development of selective small molecules targeted anticancer agents Methods: The behavior of benzoxazinone 2 towards nitrogen nucleophiles such as hydrazine hydrate, formamide, ethanolamine, aromatic amines, and thiosemcarbazide was described. The behavior of the amino quinazolinone 3 towards carbon electrophiles and P2S5 was also investigated. The antiproliferative activity of 17 new benzoxazinone derivatives was examined against the growth of three human cancer cell lines; liver HepG2, breast MCF-7, and colon HCT-29, in addition to the normal human fibroblasts WI-38 and the selectivity index was calculated. The possible molecular pathways such as the cell cycle and apoptosis were investigated. Results: Derivatives 3, 7, 8, 10, 13, and 15 had a significant (less than 10 µM) antiproliferative activity against the three cancer cell lines investigated. Derivative 7 showed the best antiproliferative profile comparable to that of doxorubicin. The selectivity index for all the effective derivatives ranged from ~5-12 folds indicating high selectivity against the cancer cells. Derivative 15 caused ~ 7-fold and 8-fold inductions in the expression of p53 and caspase3, respectively. It also caused a ~ 60% reduction in the expression of both topoisomerase II (topoII) and cyclin-dependent kinase 1 (cdk1). Derivatives 3, 7, and 8 had a similar profile; ~ 6-8-fold increases in the expression of p53 and caspase3 but these compounds were devoid of any significant effect on the expression of topoII and cdk1. Derivatives 10 and 13 were also similar and resulted in a ~6-fold elevation in the expression of caspase3, and more than 60% downregulation in the expression of topoII. The results of the gene expression of topoII and caspase 3 were confirmed by the measurement of the topoII concentration and caspase3 activity in the HepG2 cells. Conclusion: Six derivatives exerted their antiproliferative activity by arresting the cell cycle (decreasing cdk1), preventing the DNA duplication (downregulating topo II), and by inducing apoptosis (inducing p53 and caspase3). One common feature in all the six active derivatives is the presence of free amino group. These compounds have merit for further investigations.

scholarly journals Genistein Derivatives Regioisomerically Substituted at 7-O- and 4′-O- Have Different Effect on the Cell Cycle

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
A. Byczek ◽  
J. Zawisza-Puchalka ◽  
A. Gruca ◽  
K. Papaj ◽  
G. Grynkiewicz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Biological Effects ◽  
Cancer Cell Lines ◽  
Dna Lesions ◽  
Hydroxyl Group ◽  
Human Cancer Cell Lines

Our previous studies on antiproliferative properties of genistein derivatives substituted at C7 hydroxyl group of the ring A revealed some compounds with antimitotic properties. The aim of this work was to synthesize their analogues substituted at the 4′-position of the ring B in genistein and to define their antiproliferative mechanism of action in selected cancer cell linesin vitro. C4′-substituted glycoconjugates were obtained in a three-step procedure: (1) alkylation with anω-bromoester; (2) deacylation; (3) Ferrier-type rearrangement glycosylation with acylated glycals. Biological effects including antiproliferative effects of the compounds, cell cycle, DNA lesions (ATM activation, H2A.X phosphorylation, and micronuclei formation), and autophagy were studied in human cancer cell lines. Some of the tested derivatives potently inhibited cell proliferation. The presence of a substituent at the 4′-position of the ring B in genistein correlated to a p53-independent G1 cell-cycle arrest. The derivatives substituted at C4′ did not induce DNA lesions and appeared to be nongenotoxic. The tested compounds induced autophagy and caused remarkable decrease of cell volume.

scholarly journals Synthesis of Platinum(II) Complexes with Some 1-Methylnitropyrazoles and In Vitro Research on Their Cytotoxic Activity

2020 ◽  
Vol 13 (12) ◽  
pp. 433
Author(s):  
Henryk Mastalarz ◽  
Agnieszka Mastalarz ◽  
Joanna Wietrzyk ◽  
Magdalena Milczarek ◽  
Andrzej Kochel ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cell Cycle Progression ◽  
Human Cancer ◽  
Diffraction Method ◽  
Cancer Cell Lines ◽  
Human Cancer Cell Lines ◽  
Additional Information ◽  
Mcf 7

A series of eight novel platinum(II) complexes were synthesized by the reaction of the appropriate 1-methylnitropyrazole derivatives with K2PtCl4 and characterized by elemental analysis, ESI MS spectrometry, 1H NMR, 195Pt NMR, IR and far IR spectroscopy. Thermal isomerization of cis-dichloridobis(1-methyl-4-nitropyrazole)platinum(II) 1 to trans-dichloridobis(1-methyl-4-nitropyrazole)platinum(II) 2 has been presented, and the structure of the compound 2 has been confirmed by X-ray diffraction method. Cytotoxicity of the investigated compounds was examined in vitro on three human cancer cell lines (MCF-7 breast, ES-2 ovarian and A-549 lung adenocarcinomas) and their logP was measured using a shake-flask method. The trans complex 2 showed better antiproliferative activity than cisplatin for all the tested cancer cell lines. Additionally, trans-dichloridobis(1-methyl-5-nitropyrazole)platinum(II) 4 has featured a lower IC50 value than reference cisplatin against MCF-7 cell line. To gain additional information that may facilitate the explanation of the mode of action of tested compounds cellular platinum uptake, stability in L-glutathione solution, influence on cell cycle progression of HL-60 cells and ability to apoptosis induction were determined for compounds 1 and 2.

scholarly journals BRG1 mutations found in human cancer cell lines inactivate Rb-mediated cell-cycle arrest

2011 ◽  
Vol 226 (8) ◽  
pp. 1989-1997 ◽  
Author(s):  
Christopher Bartlett ◽  
Tess J. Orvis ◽  
Gary S. Rosson ◽  
Bernard E. Weissman
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Cycle Arrest

scholarly journals INDUCTION OF CELL CYCLE ARREST AND APOPTOSIS BY ORMENIS ERIOLEPIS A MORROCAN ENDEMIC PLANT IN VARIOUS HUMAN CANCER CELL LINES

2017 ◽  
Vol 14 (2) ◽  
pp. 356-373 ◽  
Author(s):  
Lamiae Belayachi ◽  
Clara Aceves-Luquero ◽  
nawel Merghoub ◽  
Silvia Fernandez de Mattos ◽  
Saaid Amzazi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Endemic Plant ◽  
Human Cancer Cell Lines ◽  
Cycle Arrest

scholarly journals Evaluation of Terpenes Psiadin, Plectranthone, and Saudinolide as Selective Anti-Cancer Agents against Hepatic Carcinoma Cells

2020 ◽  
Author(s):  
Khaled Y. Orabi ◽  
Mohamed S. Abaza ◽  
Rajaa Al-Attiyah ◽  
Yunus A. Luqmani
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Cancer Cell Lines ◽  
Chemotherapeutic Agents ◽  
Isolation And Purification

: Plant-derived terpenes have aroused considerable interest as chemotherapeutic agents for a variety of diseases. This study aimed at the isolation and purification of the scarce terpenes psiadin, plectranthone and saudinolide from their respective plants, followed by the determination of antiproliferative activity, against hepatic cancer cell lines (HepG2, Hep3B), and the potential molecular mechanisms. Time- and dose-dependent cytotoxicity, evaluated using MTT and colony-forming assays, were exhibited by psiadin and plectranthone against the cancer cells. Flow cytometry showed that these two terpenes blocked cell cycle progression and induced mitochondrial-mediated apoptosis, particularly through increased cytochrome c and disruption of mitochondrial membrane potential. Additionally, they initiated the generation of reactive oxygen species as well as inhibiting NF-B. Psiadin lowered several essential cyclins and cyclin-dependent kinases and reduced RB activation. It was concluded that psiadin, in particular, has a significant therapeutic potential with the biggest advantage of differentiating between cancer and normal cells which is acutely lacking in current cytotoxic drugs. Its precise mode of action needs further investigation but appears predominantly to cause cell cycle arrest by interfering with cyclin production. It will be important to determine, in future studies, whether these terpenes will similarly inhibit other cancer cell lines and retain its activity against tumors in vivo.

Sign in / Sign up

Export Citation Format

Share Document