The tumor-suppressive activity of melanoma differentiation-associated gene-7 (mda-7), also known as interleukin 24 (IL-24), has been shown in a spectrum of human cancer cells in vitro and in vivo. However, mechanisms responsible for antitumor activity of mda-7 in human ovarian cancer cells have not been identified. We investigated the therapeutic activity and underlying mechanisms of adenovirus-mediated mda-7 gene (Ad-mda7) transfer in human ovarian cancer cells. Ad-mda7 treatment resulted in overexpression of MDA-7/IL-24 protein in both ovarian cancer and normal ovarian epithelial cells. However, Ad-mda7 significantly (P = 0.001) inhibited cell proliferation and induced apoptosis only in tumor cells and not in normal cells. Studies addressing the mechanism of action of Ad-mda7-induced tumor cell apoptosis revealed early activation of the transcription factors c-Jun and activating transcription factor 2, which in turn stimulated the transcription of an immediate downstream target, the death-inducer Fas ligand (FasL), and its cognate receptor Fas. Associated with the activation of Fas-FasL was the activation of nuclear factor kappaB and induction of Fas-associated factor 1, Fas-associated death domain, and caspase-8. Promoter-based reporter gene analyses showed that Ad-mda7 specifically activated the Fas promoter. Inhibition of Fas using small interfering RNA resulted in a significant decrease in Ad-mda7-mediated tumor cell death. Additionally, blocking of FasL with NOK-1 antibody abrogated Ad-mda7-mediated apoptosis. Collectively, these results show that Ad-mda7-mediated killing of human ovarian cancer cells involves activation of the Fas-FasL signaling pathway, a heretofore unrecognized mediator of MDA-7 apoptosis induction.
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http://dx.doi.org/10.1158/0008-5472.CAN-04-3758 | DOI Listing |
Discov Oncol
December 2024
School of Clinical Medicine, Dali University, Dali, 671000, Yunnan, People's Republic of China.
Objective: Searching for potential biomarkers and therapeutic targets for early diagnosis of gynecological tumors to improve patient survival.
Methods: Microarray datasets of cervical cancer (CC) and ovarian cancer (OC) were downloaded from the Gene Expression Omnibus (GEO) database, then, differential gene expression between cancerous and normal tissues in the datasets was analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to screen for co-expression modules associated with CC and OC.
Biometals
December 2024
Department of Chemistry, Baba Mastnath University, Asthal Bohar, Rohtak, 124021, India.
The Schiff base metal complexes containing the transition metal ions Co(II), Ni(II) and Cu(II) were synthesized using their nitrate and acetate salts. An octahedral environment encircling metal complexes has been demonstrated by the findings of multiple spectroscopic approaches that were employed to demonstrate the structure of the metal complexes. The Coats-Redfern method of thermal analysis was employed to carry out the kinetic and thermodynamic calculations.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
University of Minnesota Twin Cities College of Science and Engineering, Chemical Engineering and Materials Science, 421 Washington Ave SE, 55455, Minneapolis, UNITED STATES OF AMERICA.
We report the development of a small molecule-based barcoding platform for pooled screening of nanoparticle delivery. Using aryl halide-based tags (halocodes), we achieve high-sensitivity detection via gas chromatography coupled with mass spectrometry or electron capture. This enables barcoding and tracking of nanoparticles with minimal halocode concentrations and without altering their physicochemical properties.
View Article and Find Full Text PDFPleura Peritoneum
December 2024
Athens Colorectal Laboratory, Athens, Greece.
ACS Omega
December 2024
Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal 700032, India.
Cancer stem cells (CSCs) are responsible for chemoresistance and tumor relapse in many solid malignancies, including lung and ovarian cancer. Ellagic acid (EA), a natural polyphenol, exhibits anticancer effects on various human malignancies. However, its impact and mechanism of action on cancer stem-like cells (CSLCs) are only partially understood.
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