32-5 |
Cyclooxygenase-2 inhibition and antiangiogenesis as molecular basis for cancer chemoprevention by some dietary phytochemicals |
Y. J. SURH1, K. S. Chun1, M. H. Chung1, K. W. Kim1, S. O. Kim1, O. H. Kim2, H. S. Jun2, and Y. G. Kwon3. (1) College of Pharmacy, Seoul National Univ., Shinlim-dong, Kwanak-ku, Seoul, 151-742, South Korea, (2) Korea Food & Drug Administration, Seoul, 122-704, South Korea, (3) Dept. of Biochemistry, Kangwon National Univ., School of Natural Sciences, Chuncheon, Kangwon-do, South Korea A wide array of anti-inflammatory substances present in dietary and medicinal plants have been reported to possess chemopreventive activities. Our recent studies have revealed that curcumin, a yellow pigment present in turmeric (Curcuma longa L., Zingiberaceae) and [6]-gingerol, a major pungent ingredient of ginger (Zingiber officinale Roscoe, Zingiberaceae), inhibit mouse skin tumor promotion, which appears to be associated with inhibition of COX-2 expression, TNF-a production, and ornithine decarboxylase activity/expression. Suppression of TPA-induced COX-2 expression by these anti-inflammatory phytochemicals appears to be mediated by targeting upstream signaling cascades that involve redox-sensitive transcription factors (e.g., NF-kB and AP-1) and mitogen-activated protein kinases, such as ERK1/2 and p38. Capsaicin, a principal pungent constituent of hot chili pepper (Capsicum annuum L., Solanaceae) with potential anti-inflammatory activity also attenuated tumor promotion and TPA-induced activation of NF-kB and AP-1 in mouse skin. Besides exerting anti-tumor promoting activity, capsaicin induces apoptosis in certain transformed (e.g., MCF10A-ras) and cancerous cells. In another study, capsaicin at 0.1 mM significantly inhibits matrix metalloproteinase-2 activity as determined by gelatin zymography, and also suppressed development of pulmonary colonization in an experimental lung metastasis assay. Intraperitoneal injection of capsaicin at 1.25 or 2.5 mg/kg inhibited expression of vescular endothelial growth factor (VEGF) and inducible nitric oxide synthase in the tumor lesions. The expression of VEGF in human vascular endothelial cells was also inhibited by capsaicin treatment. NO is known to affect tumor progression by regulating the angiogenesis, possibly through stimulation of VEGF production. We found that capsaicin inhibited production of NO and VEGF in conditioned media and expression of iNOS and COX-2 in murine peritoneal macrophages stimulated with lipopolysaccharide.
Session 32, Angiogenesis and functional foods
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