| In vitro: |
| Immunopharmacol Immunotoxicol. 2001 Feb;23(1):83-95. | | Podophyllotoxin lignans enhance IL-1beta but suppress TNF-alpha mRNA expression in LPS-treated monocytes.[Pubmed: 11322652 ] | There exists a growing body of research which indicates that antimitotics such as taxol and colchicine influence cytokine gene expression.
METHODS AND RESULTS:
In the present study we examined the effect of podophyllotoxin and six analogs on nuclear factor kappa B (NF-kappa B) activation, and on interleukin-1 beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) mRNA expression in human THP-1 monocytes. All compounds were inactive between 0.001microM and 10microM when tested alone. However, podophyllotoxin (0.1 microM) enhanced LPS-induced NF-kappa B activation and IL-1beta mRNA expression between 2 and 3-fold. In contrast, LPS-induced TNF-alpha mRNA expression was decreased between 3 and 6-fold. Comparable results were also observed with the three analogs acetylpodophyllotoxin, 4'-demethylpodophyllotoxin and alpha-peltatin. The remaining three analogs (podophyllotoxin 4-O-glucoside, beta-peltatin-beta-D-glucopyransoide and 1,2,3,4-dehydrodesoxypodophyllotoxin) were inactive. Clearly certain structural features such as the presence of a glycosidic group or ring aromatization results in loss of biological activity. Interestingly, the analogs that were inactive in our assays have also been previously shown to lack affinity for tubulin binding.
CONCLUSIONS:
These results suggest that during the initial hours of exposure to podophyllotoxin or specific analogs these compounds do not act as independent stimulants of human monocyte activation, but can selectively enhance or suppress LPS-induced cytokine gene expression. | | Plant Cell Rep. 1990 Nov;9(7):382-5. | | Production of tumour-inhibitory lignans in callus cultures of Podophyllum hexandrum.[Pubmed: 24227060] |
METHODS AND RESULTS:
Callus cultures have been established from root explants of aseptically-grown Podophyllum hexandrum seedlings.
A fully defined medium based on Gamborg's B5 salts supplemented with 2/4-dichlorophenoxyacetic acid, gibberellic acid and 6-benzylaminopurine was effective for both initiation and sustained growth of callus tissue. Cultures produced anticancer lignans podophyllotoxin, 4'-demethylpodophyllotoxin and Podophyllotoxin 4-O-glucoside at levels similar to those found in the expiant material as assayed by high performance liquid chromatography.
CONCLUSIONS:
The relative proportions of podophyllotoxin and 4'-demethyl-podophyllotoxin were markedly influenced by the presence of plant growth regulators.Particularly high levels of podophyllotoxin were associated with growth regulator induced tissue differentiation. |
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