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Benzylidene derivatives of andrographolide inhibit growth of breast and colon cancer cells in vitro by inducing G1 arrest and apoptosis

Overview of attention for article published in British Journal of Pharmacology, January 2009
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Title
Benzylidene derivatives of andrographolide inhibit growth of breast and colon cancer cells in vitro by inducing G1 arrest and apoptosis
Published in
British Journal of Pharmacology, January 2009
DOI 10.1038/bjp.2008.368
Pubmed ID
Authors

S R Jada, C Matthews, M S Saad, A S Hamzah, N H Lajis, M F G Stevens, J Stanslas

Abstract

Andrographolide, the major phytoconstituent of Andrographis paniculata, was previously shown by us to have activity against breast cancer. This led to synthesis of new andrographolide analogues to find compounds with better activity than the parent compound. Selected benzylidene derivatives were investigated for their mechanisms of action by studying their effects on the cell cycle progression and cell death. Microculture tetrazolium, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and sulphorhodamine B (SRB) assays were utilized in assessing the in vitro growth inhibition and cytotoxicity of compounds. Flow cytometry was used to analyse the cell cycle distribution of control and treated cells. CDK1 and CDK4 levels were determined by western blotting. Apoptotic cell death was assessed by fluorescence microscopy and flow cytometry. Compounds, in nanomolar to micromolar concentrations, exhibited growth inhibition and cytotoxicity in MCF-7 (breast) and HCT-116 (colon) cancer cells. In the NCI screen, 3,19-(2-bromobenzylidene) andrographolide (SRJ09) and 3,19-(3-chloro-4-fluorobenzylidene) andrographolide (SRJ23) showed greater cytotoxic potency and selectivity than andrographolide. SRJ09 and SRJ23 induced G(1) arrest and apoptosis in MCF-7 and HCT-116 cells, respectively. SRJ09 downregulated CDK4 but not CDK1 level in MCF-7 cells. Apoptosis induced by SRJ09 and SRJ23 in HCT-116 cells was confirmed by annexin V-FITC/PI flow cytometry analysis. The new benzylidene derivatives of andrographolide are potential anticancer agents. SRJ09 emerged as the lead compound in this study, exhibiting anticancer activity by downregulating CDK4 to promote a G(1) phase cell cycle arrest, coupled with induction of apoptosis.

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Mendeley readers

The data shown below were compiled from readership statistics for 70 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Malaysia 2 3%
Japan 1 1%
Unknown 67 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 16 23%
Student > Master 14 20%
Researcher 5 7%
Student > Bachelor 4 6%
Professor 4 6%
Other 9 13%
Unknown 18 26%
Readers by discipline Count As %
Medicine and Dentistry 10 14%
Pharmacology, Toxicology and Pharmaceutical Science 9 13%
Biochemistry, Genetics and Molecular Biology 8 11%
Agricultural and Biological Sciences 8 11%
Chemistry 8 11%
Other 6 9%
Unknown 21 30%