A nonpromoting phorbol from the samoan medicinal plant Homalanthus nutans inhibits cell killing by HIV-1.

Abstract

Extracts of Homalanthus nutans, a plant used in Samoan herbal medicine, exhibited potent activity in an in vitro, tetrazolium-based assay which detects the inhibition of the cytopathic effects of human immunodeficiency virus (HIV-1). The active constituent was identified as prostratin, a relatively polar 12-deoxyphorbol ester. Noncytotoxic concentrations of prostratin from greater than or equal to 0.1 to greater than 25 microM protected T-lymphoblastoid CEM-SS and C-8166 cells from the killing effects of HIV-1. Cytoprotective concentrations of prostratin greater than or equal to 1 microM essentially stopped virus reproduction in these cell lines, as well as in the human monocytic cell line U937 and in freshly isolated human monocyte/macrophage cultures. Prostratin bound to and activated protein kinase C in vitro in CEM-SS cells and elicited other biochemical effects typical of phorbol esters in C3H10T1/2 cells; however, the compound does not appear to be a tumor promoter. In skin of CD-1 mice, high doses of prostratin induced ornithine decarboxylase only to 25-30% of the levels induced by typical phorbol esters at doses 1/30 or less than that used for prostratin, produced kinetics of edema formation characteristic of the nonpromoting 12-deoxyphorbol 13-phenylacetate, and failed to induce the acute or chronic hyperplasias typically caused by tumor-promoting phorbols at doses of 1/100 or less than that used for prostratin.

• Authors: K R Gustafson, J H Cardellina 2nd, J B McMahon, R J Gulakowski, J Ishitoya, Z Szallasi, N E Lewin, P M Blumberg, O S Weislow, J A Beutler
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 35 Issue 11 Pg. 1978-86 (May 29 1992) ISSN: 0022-2623 [Print] United States
• PMID: 1597853 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Phorbol Esters
• prostratin
• Protein Kinase C
• Ornithine Decarboxylase

Topics

• Animals
• Cell Line
• Cell Survival (drug effects)
• Cytopathogenic Effect, Viral (drug effects)
• Edema (chemically induced)
• HIV-1 (drug effects)
• Humans
• Hyperplasia
• Independent State of Samoa
• Magnetic Resonance Spectroscopy
• Mice
• Monocytes (drug effects, microbiology)
• Ornithine Decarboxylase (biosynthesis)
• Phorbol Esters (chemistry, isolation & purification, pharmacology)
• Plants, Medicinal (chemistry)
• Protein Kinase C (metabolism)
• Skin (drug effects, enzymology, pathology)
• T-Lymphocytes (drug effects, microbiology)
• Virus Replication (drug effects)