stilbenes and cajanine

In the present study, we investigated the activity and modes of action of cajanin stilbene acid (CSA) and its derivatives in terms of cytotoxicity, gene expression profile, and transcription factor activity. XTT assays on MCF7 cells were performed upon treatment with CSA or derivatives. After the determination of IC50 values, gene expression profiling was performed with Agilent microarray experiments. Deregulated genes were determined with Chipster software, pathway and functional analyses were performed with Ingenuity pathway software. In order to identify the potential upstream regulators, MatInspector software was used to perform transcription factor binding motif search in the promoter regions of the deregulated genes. Molecular docking on MYC/MAX complex and reporter cell line experiments were performed to validate the MYC inhibitory activity of CSA and its derivatives. Two known MYC inhibitors: 10058-F4 and 10074-G5 were used as positive control. All compounds showed cytotoxicities in the micromolar range. Microarray analyses pointed to cell cycle, DNA damage, and DNA repair as mainly affected cellular functions. Promoter motif analysis of the deregulated genes further supported the microarray gene expression analysis results emphasizing the relevance of transcription factors regulating cell cycle and proliferation, with MYC as being the most pronounced one. Luciferase-based reporter cell line experiments and molecular docking studies yielded supportive results emphasizing the inhibitory activity of CSA and its derivatives on MYC. CSA and its derivatives are shown to be promising anticancer compounds with low toxicity. They inhibit MYC activity comparable to 10058-F4 and 10074-G5. Further studies are warranted to analyze the therapeutic applicability of these compounds in more detail.

Topics: Antineoplastic Agents; Breast Neoplasms; Diethylstilbestrol; Drug Screening Assays, Antitumor; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes, myc; Humans; MCF-7 Cells; Molecular Docking Simulation; Oligonucleotide Array Sequence Analysis; Promoter Regions, Genetic; Salicylates; Stilbenes

Cajanus cajan (L.) is a traditional Chinese herb medicine which contains a lot of potential active components. In the present study, we identified the effects of the stilbenes containing extract-fraction from C. cajan L. (sECC) on Abeta(25-35)-induced cognitive deficits, oxidative stress and cholinergic dysfunction in mice. Mice were treated with sECC (100 and 200mg/kg/d) for 1-week, and then received a single intracerebroventricular (i.c.v.) injection of Abeta(25-35) (5mug/mice). Behavioral changes and neuron apoptosis in mice were evaluated using Morris water maze and TUNEL tests. Furthermore, superoxide dismutase (SOD), choline acetyl transferase (ChAT) and acetylcholine esterase (AchE) activity in hippocampus and cortex were analyzed by spectrophotometric method. The data showed that consumption of sECC (200mg/kg) significantly ameliorated the cognitive deficits and neuron apoptosis caused by i.c.v. injection of Abeta(25-35). At the same time, the decreased SOD and ChAT activity in hippocampus and cortex were markedly increased by sECC (200mg/kg). sECC has no effect on AchE activity in hippocampus and cortex. These findings suggest that sECC may be a potential candidate for the development of therapeutic agents to manage cognitive impairment associated with Alzheimer's disease (AD) through increasing the activity of ChAT and anti-oxidative mechanism.

Topics: Acetylcholinesterase; Amyloid beta-Peptides; Animals; Antioxidants; Apoptosis; Brain; Cajanus; Cerebral Cortex; Choline O-Acetyltransferase; Cognition Disorders; Diethylstilbestrol; Female; Hippocampus; In Situ Nick-End Labeling; Maze Learning; Mice; Mice, Inbred BALB C; Neurons; Oxidative Stress; Peptide Fragments; Plant Extracts; Stilbenes; Superoxide Dismutase