Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytochrome P450 2J2 (CYP2J2) is highly expressed in human tumors and carcinoma cell lines, and has been implicated in the pathogenesis of human cancers. The aim of this study was to identify a compound that could inhibit the activity of CYP2J2, and to examine its anticancer activity. To identify CYP2J2 inhibitors, 10 terpenoids obtained from plants were screened using astemizole as a CYP2J2 probe substrate in human liver microsomes (HLMs). Of these, tanshinone IIA dose-dependently and non-competitively inhibited CYP2J2-mediated astemizole O-demethylation activity. Tanshinone IIA significantly decreased viability of human hepatoma HepG2 cells and SiHa cervical cancer cells; however, it was not cytotoxic against mouse hepatocytes. Furthermore, treatment of cells with tanshinone IIA significantly increased apoptotic cell death rate, as shown by the increase in Annexin V-stained cell populations, Bcl-2 associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio, and poly (ADP-ribose) polymerase 1 (PARP-1) cleavage in HepG2 cells. Furthermore, the results of this study showed that tanshinone IIA significantly decreased HepG2 cell-based tumor growth in nude mice in a dose-dependent manner. On the other hand, the tanshinone IIA-induced apoptotic cell death rate was significantly attenuated by enhanced up-regulation of CYP2J2 expression. Thus, our data strongly suggest that tanshinone IIA exerts its anticancer effect by inhibiting CYP2J2 activity.
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PMID:Inhibition of cytochrome P450 2J2 by tanshinone IIA induces apoptotic cell death in hepatocellular carcinoma HepG2 cells. 2620 60

Human metapneumovirus (hMPV) has been identified as a major cause of lower respiratory tract infection in children. Epidemiological and molecular evidence has highlighted an association between severe childhood respiratory viral infection and chronic lung diseases, such as asthma and chronic obstructive pulmonary disease. Currently, animal models have demonstrated the ability of hMPV to persist in vivo suggesting a role of the virus in asthma development in children. However, mechanisms involved in hMPV persistence in the respiratory tract are not yet understood. In the present study we monitored hMPV infection in human alveolar epithelial A549 cells in order to understand if the virus is able to persist in these cells upon acute infection. Our data show that hMPV initially induces an apoptotic process in A549 cells through poly (ADP-ribose) polymerase 1 cleavage, caspase-3/7 activation and Wee1 activity. The hMPV-infected cells were then able to overcome the apoptotic pathway and cell cycle arrest in G2/M by expressing B-cell lymphoma 2 and to acquire a reservoir cell phenotype with constant production of infectious virus. These findings provide evidence of the ability of hMPV to persist in alveolar epithelial cells and help in understanding the mechanisms responsible for hMPV persistence in the human respiratory tract.
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PMID:Human lung epithelial cells support human metapneumovirus persistence by overcoming apoptosis. 2961 59