Gulakowski R J, McMahon J B, Buckheit R W, Gustafson K R, Boyd M R
Laboratory of Drug Discovery Research and Development, National Cancer Institute, NCI, Frederick Cancer Research and Development Center, MD 21702-1201, USA.
Antiviral Res. 1997 Jan;33(2):87-97. doi: 10.1016/s0166-3542(96)01004-2.
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).
原锥醇是一种无肿瘤促进作用的佛波酯，在多种急性感染细胞系统中可抑制人类免疫缺陷病毒（HIV）诱导的细胞杀伤和病毒复制。细胞保护的效力和程度取决于病毒株和宿主细胞类型。原锥醇可激活两个潜伏感染细胞系中的病毒表达，但对慢性感染细胞系几乎没有影响。原锥醇导致CEM - SS和MT - 2细胞系中CD4表达呈剂量依赖性但可逆的下降。蛋白激酶C（PKC）拮抗剂星形孢菌素以剂量依赖性方式抑制了这种CD4的下调。此外，PKC激动剂苔藓抑素-1可逆转原锥醇对急性感染HIV - 1RF的CEM - SS细胞的细胞保护和细胞抑制作用。原锥醇对逆转录酶或HIV - 1蛋白酶没有影响，也不抑制gp120与CD4的结合。我们得出结论，原锥醇通过涉及PKC酶的机制抑制HIV的细胞病变效应和复制。
