A novel ATG4B antagonist inhibits autophagy and has a negative impact on osteosarcoma tumors.

Autophagy has been implicated in the progression and chemoresistance of various cancers. In this study, we have shown that osteosarcoma Saos-2 cells lacking ATG4B, a cysteine proteinase that activates LC3B, are defective in autophagy and fail to form tumors in mouse models. By combining in silico docking with in vitro and cell-based assays, we identified small compounds that suppressed starvation-induced protein degradation, LC3B lipidation, and formation of autophagic vacuoles.

Reactive oxygen species mediated calcium oxalate crystal-induced expression of MCP-1 in HK-2 cells.

Under severe hyperoxaluric conditions calcium oxalate crystals often deposit in the renal interstitium and produce localized inflammation. We have proposed that renal epithelial cells exposed to CaOx crystals produce chemoattractants such as monocyte chemoattractant protein-1 (MCP-1). MCP-1 synthesis is mediated by reactive oxygen species (ROS).

Oxalate induced expression of monocyte chemoattractant protein-1 (MCP-1) in HK-2 cells involves reactive oxygen species.

Oxalate is a toxic end product of metabolism largely because of its propensity to crystallize and form calcium oxalate, which is insoluble at physiologic pH and often deposits at very unfortunate sites, notably the kidneys. In the current study, we investigated the oxalate-induced injury and up-regulation of monocyte-chemoattractant protein-1 (MCP-1) in HK-2 cells, a proximal tubular epithelial cell line derived from normal human kidney. The cells were exposed to oxalate ions for different lengths of time.