X-Ray Crystallographic Studies of CDK2, a Basis for Cyclin-Dependent Kinase Inhibitor Design in Anti-Cancer Drug Research

The use of natural compounds is promising in approaches to prevent and treat cancer. The long-term application of most currently employed chemotherapy techniques has toxic side effects. Eugenol, a phenolic phytochemical extracted from certain essential oils, has an anti-cancer effect. The modulation of autophagy can promote either the survival or apoptosis of cancer cells. Triple-negative (MDA-MB-231) and HER2 positive (SK-BR-3) breast cancer cell lines were treated with different doses of eugenol. Apoptosis was detected by a flow-cytometry technique, while autophagy was detected by acridine orange. Real-time PCR and Western blot assays were applied to investigate the effect of eugenol on the gene and protein expression levels of autophagy and apoptotic genes. Treating cells with different concentrations of eugenol significantly inhibited cell proliferation. The protein levels of AKT serine/threonine kinase 1 (AKT), forkhead box O3 (FOXO3a), cyclin dependent kinase inhibitor 1A (p21), cyclin-dependent kinase inhibitor (p27), and Caspase-3 and -9 increased significantly in Eugenol-treated cells. Eugenol also induced autophagy by upregulating the expression levels of microtubule-associated protein 1 light chain 3 (LC3) and downregulating the expression of nucleoporin 62 (NU p62). Eugenol is a promising natural anti-cancer agent against triple-negative and HER2-positive breast cancer. It appears to work by targeting the caspase pathway and by inducing autophagic cell death.

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Application of Proteomics in the Search for Novel Proteins Associated with the Anti-cancer Effect of the Synthetic Cyclin-dependent Kinases Inhibitor, Bohemine

Technology in Cancer Research & Treatment ◽

10.1177/153303460200100405 ◽

2002 ◽

Vol 1 (4) ◽

pp. 247-256 ◽

Cited By ~ 6

Author(s):

Hana Kovarova ◽

Petr Halada ◽

Petr Man ◽

Petr Dzubak ◽

Marian Hajduch

Keyword(s):

Mass Spectrometry ◽

Cell Cycle ◽

Protein Expression ◽

Cell Line ◽

Metabolic Pathways ◽

Kinase Inhibitor ◽

A549 Cells ◽

Cyclin Dependent Kinase ◽

Cyclin Dependent Kinase Inhibitor ◽

Anti Cancer

The purpose of this study was to use the proteomics approach, which is based on high resolution two-dimensional electrophoresis coupled with multivariate correspondence analysis and mass spectrometry, to classify objectively the biochemical basis of the anti-cancer activity of the synthetic cyclin-dependent kinase inhibitor, bohemine (BOH). The changes in the cell cycle and corresponding protein composition of the A549 human lung adenocarcinoma cell line after treatment with BOH were evaluated and proteins differentially expressed in the BOH treated A549 cells, compared to the untreated A549 counterparts, were selected. Thirteen of these candidate proteins associated with the drug effects in vitro were identified by mass spectrometry. Many of these proteins fall into one of three functional categories: i) metabolic pathways (glycolysis, nucleic acid synthesis and NADPH production), ii) stress response and protein folding, and iii) cytoskeleton and exocytosis. Changes in protein expression patterns corresponded to a higher resistance of A549 lung carcinoma cells to BOH when compared to the CEM leukaemia cell line. These protein changes reflect a fine balance of the resistant versus the susceptible phenotype in response to the drug. Since BOH is a selective cyclin-dependent kinase inhibitor, changes in the protein expression pattern can be more generally associated with cell cycle regulation as evidenced by inhibition of cell cycling in A549 cells. Our conclusions further underline the importance of cell cycle control in both the cellular signalling and metabolic pathways.

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Anti-Cancer Potential of Oxialis obtriangulata in Pancreatic Cancer Cell through Regulation of the ERK/Src/STAT3-Mediated Pathway

Molecules ◽

10.3390/molecules25102301 ◽

2020 ◽

Vol 25 (10) ◽

pp. 2301 ◽

Cited By ~ 1

Author(s):

Eun-Jin An ◽

Yumi Kim ◽

Seung-Hyeon Lee ◽

Hyun Min Ko ◽

Won-Seok Chung ◽

...

Keyword(s):

Pancreatic Cancer ◽

Target Genes ◽

Nuclear Translocation ◽

Kinase Inhibitor ◽

Cyclin B1 ◽

Cyclin Dependent Kinase ◽

Cyclin Dependent Kinase Inhibitor ◽

Plant Medicine ◽

Anti Cancer ◽

M Phase

As a plant medicine, Oxalidaceae has been used to treat various diseases in Korea. However, there is little data on the anti-cancer efficacy of Oxalidaceae, particularly O. obtriangulata. This study aimed to investigate the anti-cancer effect of O. obtriangulata methanol extract (OOE) and its regulatory actions on pancreatic carcinoma. OOE showed anti-proliferative effects and induced cell death in the colony formation and cell viability assays, respectively. The Fluorescence-activated cell sorting (FACS) data confirmed that OOE significantly induced cell cycle accumulation at the G2/M phase and apoptotic effects. Additionally, OOE inhibited the activated ERK (extracellular-signal-regulated kinase)/Src (Proto-oncogene tyrosine-protein kinase Src)/STAT3 (signal transducers and activators of transcription 3) pathways including nuclear translocation of STAT3. Furthermore, suppression of Ki67, PARP(Poly ADP-ribose polymerase), caspase-3, P27(Cyclin-dependent kinase inhibitor 1B), and c-Myc as well as the STAT3 target genes CDK(cyclin-dependent kinase)1, CDK2, Cyclin B1, VEGF-1(vascular endothelial growth factor-1), MMP-9(Matrix metallopeptidase 9), and Survivin by OOE was observed in BxPC3. We speculate that these molecular actions might support an anti-cancer effect of OOE. In this study, we demonstrated that OOE may be a promising anti-cancer material and may serve as a natural therapy and alternative remedy for pancreatic cancer treatment.

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