Increased T cell cytotoxicity by Betathine™-induced upregulation of TNFα

• Published in: International journal of immunopharmacology Vol. 22; no. 3; pp. 213 - 227
• Main Authors: Dunn, Thomas M, Wormsley, Susan, Taub, Floyd E, Pontzer, Carol H
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Science 01.03.2000
• Subjects: Antineoplastic agents; Betathine; Biological and medical sciences; Cytotoxicity; General aspects; Medical sciences; Pharmacology. Drug treatments; Tumor necrosis factor alpha; Cytotoxicity; Tumor necrosis factor alpha; Betathine; Antineoplastic agent; Human; Thiol; Immune response; Monocyte; Secretion; Cytokine; Gene expression; In vitro; T-Lymphocyte; Mechanism of action; Tumor necrosis factor α; Biological receptor
• ISSN: 0192-0561; 1879-3495
• DOI: 10.1016/S0192-0561(99)00078-8

Betathine™ (BT) is a low molecular weight disulfide that has previously been shown to exhibit in vivo antitumor activity in murine myeloma and melanoma models. We have shown that BT treatment of both human T cells and monocytes is associated with an increase in surface tumor necrosis alpha (TNFα) expression. Further, in T cells and monocytes that have been stimulated with PMA and ionomycin, the addition of BT results in a dose and time dependent increase in the percentage of high TNFα-expressing cells. Unlike TNFα upregulation produced by the commonly used thiol antioxidant N-acetyl- l-cysteine (NAC), the BT-induced increase in TNFα is observed consistently in different donors. This increase in surface TNFα is associated with elevated levels of TNFα mRNA. In addition, expression of TNFα receptor I is also significantly enhanced by BT treatment. The upregulation of surface TNFα by BT has functional consequences, in that, BT-treated T cells exhibit enhanced cytotoxic activity. Thus, increased TNFα expression may be one mechanism responsible for the antineoplastic activity of BT.