Lysis of human immunodeficiency virus infected cells by TPA-type and non-TPA type tumor promoters.

We reported previously that TPA facilitates the replication of human immunodeficiency virus (HIV) and has a selective lethal effect on HIV-infected cells by a cytopathic effect induced by HIV. We have now studied the cytopathic effects of TPA-type tumor promoters (teleocidin, aplysiatoxin, and TPA) and the non-TPA type tumor promoters (palytoxin and thapsigargin) on MOLT-4/HIVHTLV-IIIB cells. All TPA-type and non-TPA type tumor promoters tested except palytoxin stimulated in HIV production three- to sevenfold, and caused more lysis of MOLT-4/HIVHTLV-IIIB cells than of the parental MOLT-4 cells. Fifty percent of the MOLT-4/HIVHTLV-IIIB cells were killed by teleocidin, aplysiatoxin, TPA and thapsigargin at concentrations of 2.0, 2.0, 1.0 and 10 ng/ml respectively, and by palytoxin at the very low concentration of 2.0 pg/ml. Moreover, combinations of one TPA-type tumor promoter and one non-TPA type tumor promoter--but not the combination of two TPA-type tumor promoters--had additive lethal effects, supporting the idea that TPA-type and non-TPA type tumor promoters exert their cytolytic effects by different mechanisms. These latter effects may be due to production of prostaglandin E2, which is commonly induced by both types of tumor promoters.