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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adjuvants, Immunologic / pharmacology*
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Antigens, CD / biosynthesis
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Antigens, CD / drug effects
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Antineoplastic Agents / pharmacology*
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Cysteamine / analogs & derivatives*
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Cysteamine / pharmacology
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Cytotoxicity, Immunologic / drug effects*
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Dose-Response Relationship, Drug
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Humans
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Ionomycin / pharmacology
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Monocytes / drug effects
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Monocytes / immunology
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RNA, Messenger / analysis
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Receptors, Tumor Necrosis Factor / biosynthesis
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Receptors, Tumor Necrosis Factor / drug effects
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Receptors, Tumor Necrosis Factor, Type I
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T-Lymphocytes / drug effects*
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T-Lymphocytes / immunology
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Tetradecanoylphorbol Acetate / pharmacology
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Time Factors
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Transforming Growth Factor beta / biosynthesis
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Tumor Necrosis Factor-alpha / biosynthesis*
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Tumor Necrosis Factor-alpha / genetics
Substances
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Adjuvants, Immunologic
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Antigens, CD
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Antineoplastic Agents
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RNA, Messenger
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Type I
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Transforming Growth Factor beta
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Tumor Necrosis Factor-alpha
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Ionomycin
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Cysteamine
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alethine
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Tetradecanoylphorbol Acetate