Zyflamend® reduces LTB4 formation and prevents oral carcinogenesis in a 712-dimethylbenzαanthracene (DMBA)-induced hamster cheek pouch model

摘要

Aberrant arachidonic acid metabolism, especially altered cyclooxygenase and 5-lipoxygenase (LOX) activities, has been associated with chronic inflammation as well as carcinogenesis in human oral cavity tissues. Here, we examined the effect of Zyflamend®, a product containing 10 concentrated herbal extracts, on development of 7,12-dimethylbenz[α]anthracene (DMBA)-induced inflammation and oral squamous cell carcinoma (SCC). A hamster cheek pouch model was used in which 0.5% DMBA was applied topically onto the left cheek pouch of male Syrian golden hamsters either three times per week for 3 weeks (short term) or 6 weeks (long term). Zyflamend was then applied topically at one of three different doses (25, 50 and 100 μl) onto the left cheek pouch three times for 1 week (short-term study) or chronically for 18 weeks. Zyflamend significantly reduced infiltration of inflammatory cells, incidence of hyperplasia and dysplastic lesions, bromodeoxyuridine-labeling index as well as number of SCC in a concentration-dependent manner. Application of Zyflamend (100 μl) reduced formation of leukotriene B4 (LTB4) by 50% compared with DMBA-treated tissues. The reduction of LTB4 was concentration dependent. The effect of Zyflamend on inhibition of LTB4 formation was further confirmed with in vitro cell-based assay. Adding LTB4 to RBL-1 cells, a rat leukemia cell line expressing high levels of 5-LOX and LTA4 hydrolase, partially blocked antiproliferative effect of Zyflamend. This study demonstrates that Zyflamend inhibited LTB4 formation and modulated adverse histopathological changes in the DMBA-induced hamster cheek pouch model. The study suggests that Zyflamend might prevent oral carcinogenesis at the post-initiation stage.