Inhibition of human papillomavirus type 16 gene expression by nordihydroguaiaretic acid plant lignan derivatives

• Published in: Antiviral research Vol. 47; no. 1; pp. 19 - 28
• Main Authors: Craigo, Jodi, Callahan, Michelle, Huang, Ru Chih C, DeLucia, Angelo L
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.07.2000; Elsevier
• Subjects: AIDS/HIV; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - pharmacology; Biological and medical sciences; Female; Gene Expression Regulation, Viral - drug effects; General pharmacology; Herpes simplex virus; HIV Long Terminal Repeat - drug effects; Human immunodeficiency virus; Human papillomavirus; Human papillomavirus 16; Humans; Larrea tridentata; lignan; Lignans - chemistry; Lignans - pharmacology; Masoprocol - analogs & derivatives; Masoprocol - pharmacology; Medical sciences; nordihydroguaiaretic acid; P97 gene; Papillomaviridae - genetics; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Plant lignan; Promoter Regions, Genetic - drug effects; Simian virus 40 - genetics; Tumor Cells, Cultured; Human papillomavirus; Larrea tridentata; Plant lignan; Enzyme; Pharmacognosy; Luciferase; Papovaviridae; Gene expression; In vitro; Biological activity; Medicinal plant; Papillomavirus; Virus; Human papillomavirus 16; Polyphenol; Reporter gene; Zygophyllaceae; Dicotyledones; Angiospermae; Plant origin; Phenols; Antiviral; Lignan; Spermatophyta; Oxidoreductases
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/S0166-3542(00)00089-9

Several methylated derivatives of a plant lignan, nordihydroguaiaretic acid (NDGA) were found to be potent anti-viral agents by suppressing Sp1 regulated transcription within the sexually transmitted viruses human immunodeficiency virus (HIV) and herpes simplex virus (HSV). A prominent Sp1 DNA binding site within many human papillomavirus (HPV) promoters has been noted to play an active role in HPV gene expression. In this report it is shown that the three NDGA derivatives, Mal.4, M 4N, and tetra-acetyl NDGA can also inhibit gene expression from the early promoter P 97 of HPV16. The drug activity on gene expression was measured after DNA transfection of recombinant vector constructs linking the viral promoter and enhancer elements to the luciferase reporter gene. Using the specific luciferase activity as the indicator of gene expression, Mal.4 and M 4N were found to be active in a dose dependent manner that is in the same range of concentrations reported for the promoters of HIV, HSV, and simian virus 40 (SV40) while tetra-acetyl NDGA was much more active in suppression of the HPV P 97 promoter activity than Mal.4 and M 4N. The drugs showed limited to no effect on gene expression driven by the adenovirus major late promoter and the cytomegalovirus (CMV) promoter. Hence, such drug derivatives may be significant in the therapy of papillomavirus infections and their associated induced human cancers.