Cannabinoid-Induced Immunogenic Cell Death of Colorectal Cancer Cells Through De Novo Synthesis of Ceramide Is Partially Mediated by CB2 Receptor.

Our recent studies have identified a link between sphingolipid metabolites and the induction of a specialized form of regulated cell death termed immunogenic cell death (ICD). We have recently demonstrated that the synthetic cannabinoid (±) 5-epi CP 55,940 (5-epi) stimulates the accumulation of ceramide (Cer), and that inhibition of sphingosine kinase 1 (SphK1) enhances Cer accumulation and ICD-induction in human colorectal cancer (CRC) cell lines. We employed flow-cytometric, western blot analyses, pharmacological inhibitors of the sphingolipid metabolic pathway and small molecule agonists and antagonists of the CB receptors to further analyze the mechanism by which 5-epi induces Cer accumulation.

Fanning the Flames of Endoplasmic Reticulum (ER) Stress: Can Sphingolipid Metabolism Be Targeted to Enhance ER Stress-Associated Immunogenic Cell Death in Cancer?

The three arms of the unfolded protein response (UPR) surveil the luminal environment of the endoplasmic reticulum (ER) and transmit information through the lipid bilayer to the cytoplasm to alert the cell of stress conditions within the ER lumen. That same lipid bilayer is the site of de novo synthesis of phospholipids and sphingolipids. Thus, it is no surprise that lipids are modulated by and are modulators of ER stress.

Characterization of Anticancer Effects of the Analogs of DJ4, a Novel Selective Inhibitor of ROCK and MRCK Kinases.

The Rho associated coiled-coil containing protein kinase (ROCK1 and ROCK2) and myotonic dystrophy-related Cdc-42 binding kinases (MRCKα and MRCKβ) are critical regulators of cell proliferation and cell plasticity, a process intimately involved in cancer cell migration and invasion. Previously, we reported the discovery of a novel small molecule (DJ4) selective multi-kinase inhibitor of ROCK1/2 and MRCKα/β. Herein, we further characterized the anti-proliferative and apoptotic effects of DJ4 in non-small cell lung cancer and triple-negative breast cancer cells.

Proteomics reveals a global phenotypic shift of NK cells in HCV patients treated with direct-acting antivirals.

Chronic hepatitis C virus (HCV) infections compromise natural killer (NK)-cell immunity. Direct-acting antivirals (DAA) effectively eliminate HCV, but the long-term effects on NK cells in cured patients are debated. We conducted a proteomic study on CD56 NK cells of chronic HCV-infected patients before and 1 year after DAA therapy.