NDLI: Inhibition of TNFα-induced iNOS expression in HSV-tk transduced 9L glioblastoma cell lines by Marasmius oreades substances through NF-κB- and MAPK-dependent mechanisms

Content Provider	Springer Nature Link
Author	Ruimi, Nili Petrova, Roumyana D. Agbaria, Riad Sussan, Sherbel Wasser, Solomon P. Reznick, Abraham Z. Mahajna, Jamal
Copyright Year	2010
Abstract	Nitric oxide (NO) is a gaseous, radical molecule that plays a role in various physiological processes. Previously, we reported that transduction of murine colon cancer cells (MC38) with herpes simplex virus thymidine kinase (HSV-tk) gene resulted in a significant over-expression of cyclooxygenase-2 (COX-2) and activation of NF-kB pathway. In this study we show that TNFα, but not LPS, was significantly able to stimulate the production of NO in HSV-tk transduced 9L glioblastoma cell lines, mediated by the up-regulation of iNOS transcript and iNOS protein. The TNFα-induced up-regulation of iNOS expression was mediated by MAPK and NF-κB signaling pathways as revealed by using selective pharmaceutical inhibitors. A culture liquid extract of the edible and medicinal mushroom Marasmius oreades that was previously shown to inhibit iNOS expression in MCF-7 was utilized to prepare fractions and evaluate their ability to affect TNFα-induced iNOS expression in HSV tk transduced 9L cell lines. While most of the tested fractions were shown to inhibit TNFα-induced iNOS expression, they targeted different signaling pathways in a selective fashion. Here, we report that fraction SiSiF1 interfered with IKBα phosphorylation and consequently interfered with NF-κB activation pathway. SiSiF1 showed minimal interference with the phosphorylation of p38 and JNK proteins. In contrast, fraction SiSiF3 selectively inhibited the phosphorylation of p38 and fractions SiSiF4 and SiSiF5 selectively inhibited the phosphorylation of JNK with no observed effect against IKBα and p38 phosphorylation. Our data illustrate the complexity of iNOS regulation in HSV tk transduced 9L cell lines and also the richness of natural products with bioactive substances that may act synergistically through different signaling pathways to affect iNOS gene expression.
Starting Page	3801
Ending Page	3812
Page Count	12
File Format	PDF
ISSN	03014851
Journal	Molecular Biology Reports
Volume Number	37
Issue Number	8
e-ISSN	15734978
Language	English
Publisher	Springer Netherlands
Publisher Date	2010-03-12
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	IκBα phosphorylation Marasmius oreades substances iNOS expression NF-κB activation pathway MAPK 9L glioblastoma cell line Animal Biochemistry Animal Anatomy / Morphology / Histology
Content Type	Text
Resource Type	Article
Subject	Genetics Medicine Molecular Biology

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