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Medicinal Plants Classification Biosynthesis and ... - Index of

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20<br />

Rosa Martha Perez Gutierrez, Adriana Maria Neira Gonzalez et al.<br />

Recently, much attention has been devoted to identifying colon cancer chemopreventive<br />

agents <strong>of</strong> dietary origin (Surth, 1999). Moreover, β-carotene supplementation reduced the rate<br />

<strong>of</strong> colon cell proliferation in patients with adenomatous polyps (Cahill et al., 1993).<br />

Concomitantly, protection by β -carotene against colon cancer was shown in animal models<br />

(Alabaster et al., 1995) as well as in cultured cells. In particular, was observed recently that<br />

β-carotene arrested the growth <strong>of</strong> different human colon adenocarcinoma cells in a manner<br />

strictly related to the cell's ability to accumulate the carotenoid <strong>and</strong> by a mechanism<br />

involving both cell cycle arrest <strong>and</strong> induction <strong>of</strong> apoptosis (Iftikhar et al., 1996).<br />

Taken together, these data raise questions about the possibility that the growth-inhibitory<br />

<strong>and</strong> proapoptotic effects <strong>of</strong> β-carotene observed in experimental <strong>and</strong> clinical studies may<br />

involve a reduction in the expression <strong>of</strong> COX-2. Therefore, Palozza et al., (2005) verifying<br />

the effect <strong>of</strong> β-carotene on the growth <strong>of</strong> human colon adenocarcinoma cells overexpressing<br />

(LS-174, HT-29, WiDr) or not expressing (HCT116) COX-2, COX-2 expression induced by<br />

the growth factor heregulin-�, which promotes COX-2 expression through the stimulation <strong>of</strong><br />

HER2/HER3 receptors, <strong>and</strong> induction <strong>of</strong> apoptosis. The downregulation <strong>of</strong> COX-2 by βcarotene<br />

occurred in both untreated <strong>and</strong> heregulin-treated cells. It was accompanied by an<br />

increased ability <strong>of</strong> cells to undergo apoptosis <strong>and</strong> by a decrease in intracellular ROS<br />

production <strong>and</strong> in the activation <strong>of</strong> ERK1/2. Moreover, cells not expressing COX-2 were<br />

insensitive to the growth-inhibitory <strong>and</strong> proapoptotic effects <strong>of</strong> the carotenoid. The<br />

suppression <strong>of</strong> COX-2 by β-carotene may represent a molecular mechanism by which this<br />

compound acts as an antitumor agent in colon carcinogenesis.<br />

Leung et al., (2008) examine the relationship between the lipid-soluble antioxidant<br />

vitamins, the extent <strong>of</strong> free radical activity, tumor stage, the systemic inflammatory response<br />

<strong>and</strong> survival in patients with colorectal cancer. In this study showed that the systemic<br />

inflammatory response was associated with a reduction <strong>of</strong> lipid-soluble antioxidant vitamins,<br />

whereas advanced tumor stage was associated with increased lipid peroxidation in patients<br />

with colorectal cancer. Of the antioxidant vitamins measured, only retinol was independently<br />

associated with cancer-specific survival.<br />

Cervical Intraepithelial Neoplasia<br />

Given the promise <strong>of</strong> diet <strong>and</strong> micronutrient supplementation on cancer chemoprevention<br />

in numerous epidemiological trials, four r<strong>and</strong>omized clinical trials using β-carotene as a<br />

possible chemopreventative agent for cervical cancer have been completed to date with<br />

mixed results (Fairleyet al., 1996).<br />

One report presents data from a 2-year, r<strong>and</strong>omized, placebo-controlled,<br />

chemoprevention trial evaluating the effect <strong>of</strong> β-carotene in the treatment <strong>of</strong> high-grade CIN<br />

(CIN 2 <strong>and</strong> 3). Intermediate biomarkers <strong>of</strong> cervical cancer risk, including grade <strong>of</strong> CIN<br />

(cervical intraepithelial neoplasia) <strong>and</strong> HPV (Human papillomavirus) presence, <strong>and</strong> risk<br />

category (high, intermediate, low, indeterminate, or none) were also evaluated. Serum <strong>and</strong><br />

vaginal micronutrient levels were measured to determine whether they were predictive <strong>of</strong><br />

lesion regression. In conclusion, cervical biopsies <strong>and</strong> the associated cell-mediated immune

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