Project description:Many anticancer agents induce apoptosis, mitotic catastrophe or cellular senescence. Here, we report the functional characterization of an experimental inducer of tumor necrosis factor (TNF)-independent necrosis, necrocide-1 (NC1). NC1 (but not its stereoisomer) killed a panel of human cancer cells (but not normal cells) at nanomolar concentrations and with a non-apoptotic, necrotic morphotype, both in vitro and in vivo. NC1-induced killing was not inhibited by caspase blockers, anti-apoptotic BCL2 overexpression or TNFα neutralization, suggesting that NC1 elicits a bona fide necrotic pathway. However, pharmacological or genetic inhibition of necroptosis, pyroptosis and ferroptosis failed to block NC1-mediated cell death. Instead, NC1 elicited reactive oxygen species (ROS) production by mitochondria, and elimination of mitochondrial DNA, quenching of mitochondrial ROS, as well as blockade of mitochondrial permeability transition with cyclosporine A, interfered with NC1-induced cell death. NC1 induced hallmarks of immunogenic cell death incurring calreticulin (CALR) exposure, ATP secretion and high mobility group box 1 (HMGB1) release. Taken together, these data identify a previously uncharacterized signaling cascade leading to an immunogenic variant of mitochondrion-regulated necrosis, supporting the notion that eliciting regulated necrosis may constitute a valid approach for anticancer therapy.
Project description:We isolated an efficient doxycycline degrading strain Chryseobacterium sp. WX1. To investigate gene expression patterns during doxycyclinedegradation by strain WX1, we conducted a comparative transcriptomic analysis using cultures of strain WX1 with and without doxycycline addition. The RNA-Seq data revealed that 90.44-96.56% of the reads mapped to the genome of Chryseobacterium sp. WX1 across all samples. Differentially expressed genes (DEGs) analysis (|log2FC| >2; p < 0.01) showed that 693 genes were significantly up-regulated and 592 genes were significantly down-regulated.
Project description:In this study, we isolated a potent doxycycline-degrading bacterium, Chryseobacterium sp. WX1, from environmental samples. To elucidate the molecular mechanisms underlying doxycycline degradation by strain WX1, we assessed and interpreted the proteomic profiles of Chryseobacterium sp. WX1 under conditions both with and without doxycycline exposure.