Increased T cell cytotoxicity by Betathine-induced upregulation of TNFalpha.

Abstract

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 (TNFalpha) 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 TNFalpha-expressing cells. Unlike TNFalpha upregulation produced by the commonly used thiol antioxidant N-acetyl-L-cysteine (NAC), the BT-induced increase in TNFalpha is observed consistently in different donors. This increase in surface TNFalpha is associated with elevated levels of TNFalpha mRNA. In addition, expression of TNFalpha receptor I is also significantly enhanced by BT treatment. The upregulation of surface TNFalpha by BT has functional consequences, in that, BT-treated T cells exhibit enhanced cytotoxic activity. Thus, increased TNFalpha expression may be one mechanism responsible for the antineoplastic activity of BT.

• Authors: T M Dunn, S Wormsley, F E Taub, C H Pontzer
• Journal: International journal of immunopharmacology (Int J Immunopharmacol) Vol. 22 Issue 3 Pg. 213-27 (Mar 2000) ISSN: 0192-0561 [Print] England
• PMID: 10685004 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adjuvants, Immunologic
• Antigens, CD
• Antineoplastic Agents
• RNA, Messenger
• Receptors, Tumor Necrosis Factor
• Receptors, Tumor Necrosis Factor, Type I
• Transforming Growth Factor beta
• Tumor Necrosis Factor-alpha
• Ionomycin
• Cysteamine
• alethine
• Tetradecanoylphorbol Acetate

Topics

• Adjuvants, Immunologic (pharmacology)
• Antigens, CD (biosynthesis, drug effects)
• Antineoplastic Agents (pharmacology)
• Cysteamine (analogs & derivatives, pharmacology)
• Cytotoxicity, Immunologic (drug effects)
• Dose-Response Relationship, Drug
• Humans
• Ionomycin (pharmacology)
• Monocytes (drug effects, immunology)
• RNA, Messenger (analysis)
• Receptors, Tumor Necrosis Factor (biosynthesis, drug effects)
• Receptors, Tumor Necrosis Factor, Type I
• T-Lymphocytes (drug effects, immunology)
• Tetradecanoylphorbol Acetate (pharmacology)
• Time Factors
• Transforming Growth Factor beta (biosynthesis)
• Tumor Necrosis Factor-alpha (biosynthesis, genetics)