scholarly journals Structure-Based Virtual Screening and Biological Evaluation of Peptide Inhibitors for Polo-Box Domain

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 107 ◽  
Author(s):  
Fang Yan ◽  
Guangmei Liu ◽  
Tingting Chen ◽  
Xiaochen Fu ◽  
Miao-Miao Niu
Keyword(s):  
Cell Cycle ◽  
Virtual Screening ◽  
Fold Increase ◽  
Pharmacophore Modeling ◽  
Biological Evaluation ◽  
Peptide Inhibitors ◽  
Regulatory Proteins ◽  
Competitive Binding Assay ◽  
M Phase ◽  
Cell Cycle Regulatory Proteins

The polo-box domain of polo-like kinase 1 (PLK1-PBD) is proved to have crucial roles in cell proliferation. Designing PLK1-PBD inhibitors is challenging due to their poor cellular penetration. In this study, we applied a virtual screening workflow based on a combination of structure-based pharmacophore modeling with molecular docking screening techniques, so as to discover potent PLK1-PBD peptide inhibitors. The resulting 9 virtual screening peptides showed affinities for PLK1-PBD in a competitive binding assay. In particular, peptide 5 exhibited an approximately 100-fold increase in inhibitory activity (IC50 = 70 nM), as compared with the control poloboxtide. Moreover, cell cycle experiments indicated that peptide 5 effectively inhibited the expression of p-Cdc25C and cell cycle regulatory proteins by affecting the function of PLK1-PBD, thereby inducing mitotic arrest at the G2/M phase. Overall, peptide 5 can serve as a potent lead for further investigation as PLK1-PBD inhibitors.

scholarly journals Antineoplastic Effects of Honokiol on Melanoma

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Ruth Guillermo-Lagae ◽  
Sreevidya Santha ◽  
Milton Thomas ◽  
Emily Zoelle ◽  
Jonathan Stevens ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Malignant Melanoma ◽  
Cell Viability ◽  
Cell Cycle Progression ◽  
Regulatory Proteins ◽  
M Phase ◽  
Cell Cycle Regulatory Proteins ◽  
In Vitro Effects

Honokiol, a plant lignan has been shown to have antineoplastic effects against nonmelanoma skin cancer developments in mice. In this study, antineoplastic effects of honokiol were investigated in malignant melanoma models. In vitro effects of honokiol treatment on SKMEL-2 and UACC-62 melanoma cells were evaluated by measuring the cell viability, proliferation, apoptosis, cell cycle analysis, and expressions of various proteins associated with cell cycle progression and apoptosis. For the in vivo study, male nude mice inoculated with SKMEL-2 or UACC-62 cells received injections of sesame oil or honokiol for two to seven weeks. In vitro honokiol treatment caused significant decrease in cell viability, proliferation, cell cycle arrest, increased apoptosis, and modulation of apoptotic and cell cycle regulatory proteins. Honokiol caused an accumulation of cells in the G2/M phase of the cell cycle in SKMEL-2 and G0/G1 phase in UACC-62 cells. An elevated level of caspases and PARP were observed in both cell lines treated with honokiol. A decrease in the expression of various cell cycle regulatory proteins was also observed in honokiol treated cells. Honokiol caused a significant reduction of tumor growth in SKMEL-2 and UACC-62 melanoma xenografts. These findings suggest that honokiol is a good candidate for further studies as a possible treatment for malignant melanoma.

scholarly journals LncRNA RP1-85F18.6 affects osteoblast cells by regulating the cell cycle

2020 ◽  
Vol 15 (1) ◽  
pp. 951-958
Author(s):  
Jiangtao Song ◽  
Wenrong Song ◽  
Lei Zhang
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cyclin A ◽  
S Phase ◽  
Cyclin B ◽  
Regulatory Proteins ◽  
Osteoblast Cell ◽  
Osteoblast Cells ◽  
M Phase ◽  
Cell Cycle Regulatory Proteins

AbstractA lncRNA RP1-85F18.6 was reported to affect cell growth by regulating the cell cycle. Here we tested whether it affects the proliferation of osteoblast cells by regulating the cell cycle. We determined the expression of RP1-85F18.6 in two osteoblast cell lines hFOB and HOB by qPCR. Then we knocked down or overexpressed RP1-85F18.6 in hFOB and tested the alteration of viability, cell cycle, and cell cycle regulatory proteins. Results showed that both hFOB and HOB expressed RP1-85F18.6. The knockdown of RP1-85F18.6 decreased the viability of hFOB, while the overexpression of it increased the viability. Higher expression of RP1-85F18.6 results in higher cell viability. The knockdown of RP1-85F18.6 caused an increase in the S phase cells and a decrease in the G2/M phase cells. The overexpression of RP1-85F18.6 caused a decrease in the S phase cells and an increase in the G2/M phase cells. The knockdown of RP1-85F18.6 decreased cyclin A, cdk1, E2F, cyclin B, p53, and p21, whereas the overexpression of RP1-85F18.6 increased cyclin A, cdk1, E2F, cyclin B, p53, and p21. This study demonstrated that RP1-85F18.6 is expressed in osteoblast cell lines hFOB and HOB. RP1-85F18.6 affects the proliferation of osteoblasts by regulating the cell cycle.

Hybridized Quinoline Derivatives as Anticancer Agents: Design, Synthesis, Biological Evaluation and Molecular Docking

2019 ◽  
Vol 19 (4) ◽  
pp. 439-452 ◽  
Author(s):  
Mohamed R. Selim ◽  
Medhat A. Zahran ◽  
Amany Belal ◽  
Moustafa S. Abusaif ◽  
Said A. Shedid ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Anticancer Agents ◽  
Caspase 3 ◽  
Biological Evaluation ◽  
Tubulin Polymerization ◽  
Design Synthesis ◽  
Chemical Structures ◽  
M Phase ◽  
Induced Apoptosis ◽  
Derivatives Of

Objective: Conjugating quinolones with different bioactive pharmacophores to obtain potent anticancer active agents. Methods: Fused pyrazolopyrimidoquinolines 3a-d, Schiff bases 5, 6a-e, two hybridized systems: pyrazolochromenquinoline 7 and pyrazolothiazolidinquinoline 8, different substituted thiazoloquinolines 13-15 and thiazolo[3,2-a]pyridine derivatives 16a-c were synthesized. Their chemical structures were characterized through spectral and elemental analysis, cytotoxic activity on five cancer cell lines, caspase-3 activation, tubulin polymerization inhibition and cell cycle analysis were evaluated. Results: Four compounds 3b, 3d, 8 and 13 showed potent activity than doxorubicin on HCT116 and three compounds 3b, 3d and 8 on HEPG2. These promising derivatives showed increase in the level of caspase-3. The trifloromethylphenyl derivatives of pyrazolopyrimidoquinolines 3b and 3d showed considerable tubulin polymerization inhibitory activity. Both compounds arrested cell cycle at G2/M phase and induced apoptosis. Conclusion: Compounds 3b and 3d can be considered as promising anticancer active agents with 70% of colchicine activity on tubulin polymerization inhibition and represent hopeful leads that deserve further investigation and optimization.

scholarly journals Association of the Cell Cycle Regulatory Proteins p45SKP2and CksHs1

2001 ◽  
Vol 276 (27) ◽  
pp. 25030-25036 ◽  
Author(s):  
Lı́dia Mongay ◽  
Susana Plaza ◽  
Elena Vigorito ◽  
Carles Serra-Pagès ◽  
Jordi Vives
Keyword(s):  
Cell Cycle ◽  
Regulatory Proteins ◽  
Cell Cycle Regulatory Proteins

Apoptosis and cell-cycle regulatory proteins in colorectal carcinoma: relationship to tumour stage and patient survival

2001 ◽  
Vol 194 (4) ◽  
pp. 436-443 ◽  
Author(s):  
Mohamed A. Elkablawy ◽  
Perry Maxwell ◽  
Kate Williamson ◽  
Neil Anderson ◽  
Peter W. Hamilton
Keyword(s):  
Cell Cycle ◽  
Colorectal Carcinoma ◽  
Patient Survival ◽  
Regulatory Proteins ◽  
Tumour Stage ◽  
Cell Cycle Regulatory Proteins

Cell cycle regulatory proteins in renal disease: role in hypertrophy, proliferation, and apoptosis

2000 ◽  
Vol 278 (4) ◽  
pp. F515-F529 ◽  
Author(s):  
Stuart J. Shankland ◽  
Gunter Wolf
Keyword(s):  
Cell Cycle ◽  
Renal Function ◽  
Renal Disease ◽  
Cell Injury ◽  
Critical Role ◽  
Regulatory Proteins ◽  
Specific Cell ◽  
Cell Cycle Proteins ◽  
Proliferation And Apoptosis ◽  
Cell Cycle Regulatory Proteins

The response to glomerular and tubulointerstitial cell injury in most forms of renal disease includes changes in cell number (proliferation and apoptosis) and cell size (hyerptrophy). These events typically precede and may be reponsible for the accumulation of extracellular matrix proteins that leads to a decrease in renal function. There is increasing evidence showing that positive (cyclins and cyclin-dependent kinases) and negative (cyclin-dependent kinase inhibitors) cell cycle regulatory proteins have a critical role in regulating these fundamental cellular responses to immune and nonimmune forms of injury. Data now show that altering specific cell cycle proteins affects renal cell proliferation and improves renal function. Equally exciting is the expanding body of literature showing novel biological roles for cell cycle proteins in the regulation of cell hypertrophy and apoptosis. With increasing understanding of the role for cell cyle regulatory proteins in renal disease comes the hope for potential therapeutic inverventions.

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