Carcinogenesis Advance Access originally published online on August 6, 2008
Carcinogenesis 2008 29(11):2182-2189; doi:10.1093/carcin/bgn181
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Zyflamend® reduces LTB4 formation and prevents oral carcinogenesis in a 7,12-dimethylbenz[
]anthracene (DMBA)-induced hamster cheek pouch model
Department of Experimental Therapeutics The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
1 Department of Oral Medicine Beijing Hospital for Stomatology, Capital Medical University, Beijing 100050, People’s Republic of China
2 Cancer Research Program, Julius L.Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA
* To whom correspondence should be addressed. Department of Experimental Therapeutics, Unit 601, The University of Texas MD Anderson Cancer Center, 8000 El Rio Street, Houston, TX 77054, USA. Tel: +1 713 563 7543; Fax: +1 713 563 9093; Email: rnewman{at}mdanderson.org
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[
]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.
Abbreviations: AA, arachidonic acid; COX, cyclooxygenase; DMBA, 7,12-dimethylbenz[]anthracenene; HETE, hydroeicosatetraenoic acid; 13-HODE, 13-hydroxyoctadeca-9Z, 11E-dienoic acid; LOX, lipoxygenase; LTB4, leukotriene B4; MS, mass spectrometry; PBS, phosphate-buffered saline; PGE2, prostaglandin E2; SCC, squamous cell carcinoma
Received March 6, 2008; revised August 1, 2008; accepted August 1, 2008.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. L. L. Bachi, F. J. K. Kim, S. Nonogaki, C. R. W. Carneiro, J. D. Lopes, M. G. Jasiulionis, and M. Correa Leukotriene B4 Creates a Favorable Microenvironment for Murine Melanoma Growth Mol. Cancer Res., September 1, 2009; 7(9): 1417 - 1424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-L. Chung, M.-Y. Lee, and N. N.M. Pui Epigenetic therapy using the histone deacetylase inhibitor for increasing therapeutic gain in oral cancer: prevention of radiation-induced oral mucositis and inhibition of chemical-induced oral carcinogenesis Carcinogenesis, August 1, 2009; 30(8): 1387 - 1397. [Abstract] [Full Text] [PDF]
|
|