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Benzisothiazolone Derivatives Exhibit Cytotoxicity in Hodgkin's Lymphoma Cells through NF-ҡB Inhibition and are Synergistic with Doxorubicin and Etoposide.

07:00 EST 12th February 2020 | BioPortfolio

Summary of "Benzisothiazolone Derivatives Exhibit Cytotoxicity in Hodgkin's Lymphoma Cells through NF-ҡB Inhibition and are Synergistic with Doxorubicin and Etoposide."

We have investigated the NF-ҡB inhibitory role of three Benzisothiazolone (BIT) derivatives (1, 2 and 3) in Hodgkin's Lymphoma cells (L428) which constitutively express activated NF-ҡB. All three compounds show dose dependent NF-ҡB inhibition (78.3, 70.7 and 34.6%) in a luciferase reporter gene assay and are cytotoxic at IC50 values of 3.3µg/ml, 4.35µg/ml and 13.8µg/ml respectively by XTT assay. BIT 1 and BIT 2 (but not BIT 3) suppress both NF-ҡB subunits p50 and p65 in cytoplasmic and nuclear extracts in a concentration dependent manner. Furthermore, BIT 1 shows moderate synergistic effect with the standard chemotherapy drugs etoposide, and doxorubicin, whereas BIT 2 and 3 showed moderate additive effect to antagonistic effect. Cisplatin exhibited antagonist effect for all the compounds tested under various concentrations, except in the case of 1.56µg/ml of BIT 3 with 0.156µg/ml of cisplatin. The compounds also inhibit the migration of adherent human lung adenocarcinoma cells (A549) cells in vitro. We conclude that especially BIT 1 and BIT 2 have in vitro anti-inflammatory and anti-cancer activity, with future potential therapeutic use.

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Name: Anti-cancer agents in medicinal chemistry
ISSN: 1875-5992
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Medical and Biotech [MESH] Definitions

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A form of non-Hodgkin lymphoma having a usually diffuse pattern with both small and medium lymphocytes and small cleaved cells. It accounts for about 5% of adult non-Hodgkin lymphomas in the United States and Europe. The majority of mantle-cell lymphomas are associated with a t(11;14) translocation resulting in overexpression of the CYCLIN D1 gene (GENES, BCL-1).

Any of a group of malignant tumors of lymphoid tissue that differ from HODGKIN DISEASE, being more heterogeneous with respect to malignant cell lineage, clinical course, prognosis, and therapy. The only common feature among these tumors is the absence of giant REED-STERNBERG CELLS, a characteristic of Hodgkin's disease.

A systemic, large-cell, non-Hodgkin, malignant lymphoma characterized by cells with pleomorphic appearance and expressing the CD30 ANTIGEN. These so-called "hallmark" cells have lobulated and indented nuclei. This lymphoma is often mistaken for metastatic carcinoma and MALIGNANT HISTIOCYTOSIS.

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