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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Apoptosis, Butyrates, Caco-2 Cells, Cell Line, Tumor, Colonic Neoplasms, Cytokine TWEAK, Drug Synergism, HT29 Cells, Humans, Interferon-gamma, Leucine, Ligands, Membrane Potential, Mitochondrial, Mitochondria, PPAR gamma, Prostaglandin D2, Thiazolidinediones, Tumor Necrosis Factors.
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Does pPARgamma ligand 15-deoxy-delta 12,14-prostaglandin J2 sensitize human colon carcinoma cells to TWEAK-induced apoptosis? Context: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) has been shown to induce colon cancer cell apoptosis in the presence of interferon-gamma. We hypothesized that co-treatment using TWEAK with other pro-apoptosis agents could sensitize death receptor-resistant colon cancer cells. The effects of chemopreventive agents and TWEAK on cell death and apoptosis were determined using propidium iodide (PI) exclusion and M30 CytoDEATH. We found that 15d-PGJ(2) sensitizes colon cancer cells to TWEAK-induced apoptosis. Caspase inhibition reduced 15d-PGJ(2)-, but not 15d-PGJ(2)+TWEAK-induced apoptosis. 15d-PGJ(2) promoted reactive oxygen species (ROS) production and dissipation of mitochondrial potential (DeltaPsi(m)) that were more marked with combined treatment. ROS, DeltaPsi(m) and cell death were partially normalized by the antioxidant N-acetylcysteine. TWEAK induced nuclear factor-kappa B activation, which was attenuated by 15d-PGJ(2). 15d-PGJ(2) reduced the expression of the anti-apoptotic proteins BCL-X(L) and MCL-1, while increasing BAX and translocation of cytochrome c and apoptosis-inducing factor.
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15d-PGJ(2) sensitized cancer cells to TWEAK-induced apoptosis through an ROS-dependent cell death pathway and may have chemotherapeutic utility as an apoptosis-enhancing agent. Final Decision: yes