https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

Anti-cancer chalcones: Structural and molecular target perspectives.

Mesangial cells-mediated glomerulonephritis is a frequent cause of end-stage renal disease. Here, we show that celastrol is effective in treating both reversible and irreversible mesangioproliferative glomerulonephritis in rat models, but find that its off-target distributions cause severe systemic toxicity. We thus target celastrol to mesangial cells using albumin nanoparticles. Celastrol-albumin nanoparticles crosses fenestrated endothelium and accumulates in mesangial cells, alleviating proteinuria, inflammation, glomerular hypercellularity, and excessive extracellular matrix deposition in rat anti-Thy1.1 nephritis models. Celastrol-albumin nanoparticles presents lower drug accumulation than free celastrol in off-target organs and tissues, thereby minimizing celastrol-related systemic toxicity. Celastrol-albumin nanoparticles thus represents a promising treatment option for mesangioproliferative glomerulonephritis and similar glomerular diseases.

/pdf/targeted-delivery-of-celastrol-to-mesangial-cells-is-4vjywtj2ox.pdf

Targeted delivery of celastrol to mesangial cells is effective against mesangioproliferative glomerulonephritis.

Quinolone hybrids and their anti-cancer activities: An overview.

4-Nonylphenol induces apoptosis, autophagy and necrosis in Sertoli cells: Involvement of ROS-mediated AMPK/AKT-mTOR and JNK pathways.

Quinolone analogue inhibits tubulin polymerization and induces apoptosis via Cdk1-involved signaling pathways.

Ilimaquinone, a marine sponge metabolite, displays anticancer activity via GADD153-mediated pathway.

BACKGROUND

Chalcones are contained in fruits and vegetables, and have been suggested to display anticancer activities. In this study, the anticancer mechanism of WJ9708011 (a methoxychalcone derivative) was delineated in human prostate cancer cells.



METHOD

Cell proliferation was examined by sulforhodamine B and clonogenic assays. Cell-cycle progression and mitochondrial membrane potential (ΔΨm) were detected by flow cytometric analysis. Expressions of protein and mRNA were detected by Western blot and RT-PCR technique, respectively. The protein synthesis was examined by [3H]leucine incorporation assay. The overexpression or knockdown techniques for specific target protein were also used in this study.



RESULTS

WJ9708011 induced time- and concentration-dependent G1 arrest of the cell cycle and subsequent apoptosis in human prostate cancer cells. The G1-arrest effect was confirmed by down-regulated expressions of several G1-phase regulators, including cyclin D1, cyclin E, cyclin-dependent kinase (Cdk)-4, Cdk2, phospho-RB, E2F-1, and Cdc25A. The mRNA expressions of cyclin D1 and cyclin E were also inhibited through the suppression of NF-κB. WJ9708011 blocked the protein synthesis and inhibited mammalian target of rapamycin (mTOR) signaling pathways. The suppression of mTOR pathways were irrespective of Akt- and AMPK-activated protein kinase (AMPK), but were attributed to mitochondrial stress, in which the down-regulation of survivin protein level may play a crucial role.



CONCLUSIONS

The data suggest that WJ9708011 induces transcriptional and translational suppression of cell-cycle regulators that might be through Akt- and AMPK-independent loss of ΔΨm and inhibition of mTOR signaling pathway, leading to G1 arrest of the cell cycle and subsequent apoptotic cell death. Prostate 70:1295–1306, 2010. © 2010 Wiley-Liss, Inc.

Methoxychalcone induces cell-cycle arrest and apoptosis in human hormone-resistant prostate cancer cells through PI 3-kinase-independent inhibition of mTOR pathways

Pin Hsuan Lu

Papers

Quinolone analogue inhibits tubulin polymerization and induces apoptosis via Cdk1-involved signaling pathways.

Ilimaquinone, a marine sponge metabolite, displays anticancer activity via GADD153-mediated pathway.

Methoxychalcone induces cell-cycle arrest and apoptosis in human hormone-resistant prostate cancer cells through PI 3-kinase-independent inhibition of mTOR pathways