The HIV-1
Tat protein has been directly implicated in the pathogenesis of
AIDS-related
Kaposi's sarcoma (KS); however, its effects on KS spindle-shaped and endothelial cell apoptosis are largely unexplored. Since susceptibility to apoptosis is relevant for
tumor development and response to
therapy, we investigated the effects of Tat on KS and endothelial cell survival from apoptosis. The effect of Tat was evaluated in three KS cell lines (KS-imm, KS-C1, and KS-L3) exposed to the
chemotherapy agent
vincristine, currently used for the treatment of this
tumor, and in human umbilical vein-derived endothelial cells (HUVECs) induced to undergo apoptosis by serum withdrawal. Apoptosis was assessed by enzymatic assays, microscopic examination of
chromatin and cytoskeleton, evaluation of plasma membrane integrity and subdiploid
DNA content, TUNEL assays, and measurement of
caspase-3 activity. Tat, in a dose-dependent manner, protected the three KS cell lines and HUVECs from apoptosis induced by
vincristine or serum
starvation, respectively. This effect appeared to be independent of modulation of Fas, Bcl-2, or Bax expression. In contrast, Tat upregulated Bcl-X(L) expression and induced a relevant decrease in
caspase-3 activity in
vincristine-treated KS cells. Taken together, these results suggest that the HIV-1
Tat protein may factor KS development and progression by sustaining endothelial and transformed cell survival.