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

Background and purpose: 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. Experimental approach: 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. Key results: 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 G1 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. Conclusion and implications: 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 G1 phase cell cycle arrest, coupled with induction of apoptosis

Visual Informatics: Sustaining Research and Innovations. Second International Visual Informatics Conference, IVIC 2011, Selangor, Malaysia, November 9-11, 2011, Proceedings, Part II

Evaluation technique for Educational Computer Games (ECG) known as PHEG (consist of 5 heuristics and 37 subheuristics) was developed based on the needs to evaluate the usability of Educational Computer Games (Usa-ECG). Heuristic based concept was used in the development of PHEG. The fundamental issue of PHEG is to help evaluators in evaluating ECG in order to detect Usa-ECG through formative evaluation. At the end of the ECG development, it should be able to integrate educational elements, content, multimedia and it is playable to users with pleasant interface. PHEG was developed through the involvement of expert and verified by prominent experts. To further explore the importance of PHEG, Analytic Hierarchy Process (AHP) was performed by 15 experts from various fields. Result shows that Interface heuristic (40.8) is selected to be the most important heuristic in evaluating Usa-ECG. The second important heuristic is educational element (25.44) followed by Content (14.57), Playability (11.2) and Multimedia (8) heuristic. © 2011 Springer-Verlag