Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tetrandrine (TET), a bis-benzylisoquinoline alkaloid isolated from the dried root of Hang-Fang-Chi (Stephania tetrandra S. Moore), is well known to possess activities including antioxidant, anti-inflammation, anti-fibrotic and anticancer. It is used clinically to treat hypertension and silicosis. In the present study, the anti-proliferative and apoptotic effects of TET were evaluated on three different hepatoma cell lines, namely Hep G2, PLC/PRF/5 and Hep 3B. Using XTT assay, results showed that the IC50 values of TET were 4.35 microM for Hep G2, 9.44 microM for PLC/PRF/5 and 10.41 microM for Hep 3B cells. The CC50 of TET against BNL-CL.2 mouse normal liver cells was 31.12 microM. Interestingly, TET exhibited a lower IC50 value and better selectivity against Hep G2 and PLC/PRF/5 cells than cisplatin. Microscopic observation study, DNA fragmentation assay and flow cytometric analysis further supported apoptotic effect of TET on both PLC/PRF/5 and Hep 3B cells. The cell cycle of PLC/PRF/5 treated with TET appeared to arrest at G2/M phase in a dose-dependent manner, whereas no effect was noted on the cell cycle of Hep 3B cells. The present study concludes that TET exhibited anti-proliferative effect on Hep G2, PLC/PRF/5 and Hep 3B cells in a dose-dependent manner. TET also possesses a lower IC50 and better SI value than cisplatin against Hep G2 and PLC/PRF/5 cells. The effect of TET on cell cycle progression was found to vary with the type of hepatoma cells, suggesting the genetic make-up of the cells play an important role in the response to drug treatment.
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PMID:Antiproliferative and apoptotic effects of tetrandrine on different human hepatoma cell lines. 1643 45

Silica particle-associated inflammation is implicated in the genesis of several pulmonary diseases, including silicosis and lung cancer. In this study we investigated the role of phosphatidylcholine-specific phospholipase C (PC-PLC) in silica-stimulated induction of TNF-alpha and IL-1beta and how PC-PLC activity is regulated by silica in a rat alveolar macrophage model. We demonstrated that inhibition of PC-PLC, which was achieved with tricychodecan-9-yl-xanthate (D609), blocked the silica-stimulated induction of TNF-alpha and IL-1beta in alveolar macrophage, suggesting that PC-PLC is involved in the silica-associated inflammatory response. PC-PLC activity was increased significantly by silica exposure, and this could be inhibited by MnTBAP, which catalyzes both the dismutation of O2.- to O2 and H2O2 and the dismutation of H2O2 to O2 and H2O, revealing that PC-PLC activity is regulated in a redox-dependent manner. This is further confirmed by the finding that PC-PLC activity was increased by exogenous H2O2. The intracellular calcium chelator BAPTA blocked the H2O2-increased PC-PLC activity, while the calcium ionophore, A23187, enhanced PC-PLC activity. The data indicate that PC-PLC plays critical roles in the silica-associated inflammatory response and that PC-PLC is regulated through redox- and calcium-dependent manners in alveolar macrophages.
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PMID:Silica induces macrophage cytokines through phosphatidylcholine-specific phospholipase C with hydrogen peroxide. 1715 58