Novel cancer chemopreventive effects of a flavonoid antioxidant silymarin: inhibition of mRNA expression of an endogenous tumor promoter TNF alpha.

Abstract:

:In this study we describe exceptionally high protective effects of silymarin, a flavonoid antioxidant isolated from milk thistle, against 12-O-tetradecanoylphorbol 13-acetate (TPA)- and okadaic acid (OA)-caused tumor promotion in SENCAR mouse skin. Pre-application of silymarin to that of TPA in 7, 12-dimethylbenz(a)anthracene (DMBA)-initiated mouse skin resulted in almost complete protection in terms of tumor incidence (85%) as well as multiplicity (94%). In OA-caused tumor promotion studies, application of silymarin prior to that of OA in DMBA-initiated mouse skin resulted in a complete protection against tumorigenicity. We next assessed the effect of silymarin on TPA- and OA-caused induction of mRNA expression of tumor necrosis factor alpha (TNF alpha) which is an endogenous tumor promoter and a central mediator of tumor promotion in vivo in the case of both TPA and OA tumor promotion. Topical application of silymarin on mouse skin prior to that of TPA or OA resulted in a highly significant to complete inhibition in a dose-dependent manner against both TPA- and OA-caused induction of TNF alpha mRNA expression in mouse epidermis. These results indicate that silymarin exerts novel chemopreventive effects against tumorigenicity by inhibiting endogenous tumor promoter TNF alpha. Additional studies are warranted in other tumor models to further evaluate the cancer chemopreventive effect of silymarin and to define the involvement of TNF alpha as a molecular target for such an effect.

authors

Zi X,Mukhtar H,Agarwal R

doi

10.1006/bbrc.1997.7375

subject

Has Abstract

pub_date

1997-10-09 00:00:00

pages

334-9

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(97)97375-7

journal_volume

239

pub_type

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