scholarly journals Inhibition of drug resistance in two cancer cell lines(MDR and A2780CIS) in vitro; and the role of selected single nucleotide polymorphisms in cancer

2012 ◽  
Author(s):  
Julianna Serly
Keyword(s):  
Drug Resistance ◽  
Single Nucleotide Polymorphisms ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

scholarly journals Inhibition of Nek2 by Small Molecules Affects Proteasome Activity

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Lingyao Meng ◽  
Kent Carpenter ◽  
Alexis Mollard ◽  
Hariprasad Vankayalapati ◽  
Steven L. Warner ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Multiple Myeloma ◽  
Drug Resistance ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Cycle Progression ◽  
Cancer Cell Lines ◽  
Proteasome Activity ◽  
Cell Cycle Regulators

Background. Nek2 is a serine/threonine kinase localized to the centrosome. It promotes cell cycle progression from G2 to M by inducing centrosome separation. Recent studies have shown that high Nek2 expression is correlated with drug resistance in multiple myeloma patients.Materials and Methods. To investigate the role of Nek2 in bortezomib resistance, we ectopically overexpressed Nek2 in several cancer cell lines, including multiple myeloma lines. Small-molecule inhibitors of Nek2 were discovered using an in-house library of compounds. We tested the inhibitors on proteasome and cell cycle activity in several cell lines.Results. Proteasome activity was elevated in Nek2-overexpressing cell lines. The Nek2 inhibitors inhibited proteasome activity in these cancer cell lines. Treatment with these inhibitors resulted in inhibition of proteasome-mediated degradation of several cell cycle regulators in HeLa cells, leaving them arrested in G2/M. Combining these Nek2 inhibitors with bortezomib increased the efficacy of bortezomib in decreasing proteasome activityin vitro. Treatment with these novel Nek2 inhibitors successfully mitigated drug resistance in bortezomib-resistant multiple myeloma.Conclusion. Nek2 plays a central role in proteasome-mediated cell cycle regulation and in conferring resistance to bortezomib in cancer cells. Taken together, our results introduce Nek2 as a therapeutic target in bortezomib-resistant multiple myeloma.

scholarly journals Cellular discrimination using in vitro Raman micro spectroscopy: the role of the nucleolus

The Analyst ◽  
2015 ◽  
Vol 140 (17) ◽  
pp. 5908-5919 ◽  
Author(s):  
Z. Farhane ◽  
F. Bonnier ◽  
A. Casey ◽  
A. Maguire ◽  
L. O'Neill ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
High Specificity ◽  
Cancer Cell Lines ◽  
Cellular Organelle ◽  
Specificity And Sensitivity

Raman micro spectroscopy is employed to discriminate between cell lines. Results show the importance of the nuclear sub-cellular organelle, the nucleoli, to differentiate between cancer cell lines with high specificity and sensitivity.

Synthesis, antibacterial, and cytotoxicity evaluation of oleanolic acid-4-aminoquinoline based hybrid compounds

2021 ◽  
Vol 16 ◽  
Author(s):  
Vuyolwethu Khwaza ◽  
Opeoluwa O. Oyedeji ◽  
Blessing A. Aderibigbe ◽  
Eric Morifi ◽  
Y.T. Fonkui ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Lines ◽  
Oleanolic Acid ◽  
Cancer Cell ◽  
Antimicrobial Agents ◽  
Klebsiella Oxytoca ◽  
Cancer Cell Lines ◽  
Hybrid Compounds ◽  
Microbial Infections

Aim: To prepare a class of oleanolic-based compounds. Background: Conventional drugs used to treat infectious diseases suffer from limitations such as drug toxicity and drug resistance. The resistance of microbes to antimicrobial agents is a significant challenge in treating microbial infections. Combining two or more drugs with different modes of action to treat microbial infections results in a delay in developing drug resistance by the microbes. However, it is challenging to select the appropriate choice of drugs for combination therapy due to the differences in stability and pharmacokinetic profile of the drugs.Therefore, developing hybrid compounds using the existing drugs is a promising approach to design effective antimicrobial agents. Objectives: To prepare oleanolic-based hybrid compounds followed by characterization, in vitro antibacterial, and cytotoxicity evaluation. Methods:: Oleanolic acid-4-aminoquinoline-based hybrid compounds weresynthesized via esterification and amidation. The compounds werecharacterized using FTIR, NMR, and UHPLC-HRMS. Oleanolic acid was isolated from the flower buds of Syszygium aromaticum (L.) Merr. &.Perry, a specie from Kingdom Plantae, order Mytales in Myrtaceae family. Their antibacterial and cytotoxicity activity was determined against selected strains of bacteria assessed using the microdilution assay and sulforhodamine B assay against selected cancer cell lines. Results: The synthesized hybrid compounds exhibited significant antibacterial activity against the Gram-positive bacteria Enterococcus faecalis (ATCC13047), Bacillus subtilis (ATCC19659), Staphylococcus aureus as well as Gram-negative bacteria,Klebsiella oxytoca (ATCC8724), Escherischia coli (ATCC25922), and Proteus vulgaris (ATCC6380)with minimum inhibitory concentrations of 1.25 mg/mLcompared to oleanolic acid (2.5 mg/mL). Compounds 13 and 14 displayed significant cytotoxic effectsin vitro against the cancer cell lines (MCF-7 and DU 145) compared to the oleanolic acid (IC50 ˃ 200 µM). Conclusion: The present study revealed that the modification of C28 of OA enhanced its biological properties.

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