Antireplicative and anticytopathic activities of prostratin, a non-tumor-promoting phorbol ester, against human immunodeficiency virus (HIV).
Prostratin, a non-tumor-promoting phorbol ester, inhibited human immunodeficiency virus (HIV)-induced cell killing and viral replication in a variety of acutely-infected cell systems. The potency and degree of cytoprotection was dependent on both viral strain and host cell type. Prostratin activated viral expression in two latently-infected cell lines, but had little or no effect on chronically-infected cell lines. Prostratin caused a dose-dependent, but reversible, decrease in CD4 expression in the CEM-SS and MT-2 cell lines. This down-regulation of CD4 was inhibited in a dose-dependent manner by the protein kinase C (PKC) antagonist, staurosporine. In addition, the cytoprotective and cytostatic effects of prostratin in CEM-SS cells acutely infected with HIV-1RF were reversed by bryostatin-1, a PKC agonist. Prostratin had no effect on reverse transcriptase or HIV-1 protease, nor did it inhibit the binding of gp120 to CD4. We conclude that prostratin inhibits HIV cytopathicity and replication through mechanism(s) involving PKC enzyme(s).
Gulakowski
R J
RJ
Laboratory of Drug Discovery Research and Development, National Cancer Institute, NCI, Frederick Cancer Research and Development Center, MD 21702-1201, USA.
McMahon
J B
JB
Buckheit
R W
RW
Gustafson
K R
KR
Boyd
M R
MR
D019380:Anti-HIV Agents / Q000494:pharmacology*; D054713:Bryostatins; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D015536:Down-Regulation; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D018942:Macrolides; D010703:Phorbol Esters / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D054713:Bryostatins; D015704:CD4 Antigens; D007783:Lactones; D018942:Macrolides; D010703:Phorbol Esters; C046785:bryostatin 1; C070999:prostratin