Increased T cell cytotoxicity by Betathine super(TM)-induced upregulation of TNF alpha

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