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Copyright by Eunyoung Park 2007 - The University of Texas at Austin

Copyright by Eunyoung Park 2007 - The University of Texas at Austin

FIGURE 4.5. RETINOL AND

FIGURE 4.5. RETINOL AND WORTMANNIN EXHIBIT SIMILAR ELECTROSTATIC POTENTIAL SURFACES. Electrostatic potential surfaces for (A) wortmannin, (B) retinol and (C) a PI fragment were calculated as described in the Materials and Methods section. In all three panels purple wire frames indicate areas of negative electrostatic potential whereas green indicates positive potential. Surfaces are shown over a tube structure for the conformation with carbon atoms in blue, oxygen atoms in red, hydrogen atoms in white and phosphorus atoms in yellow. Arrows indicate areas associated with either reactive hydrogen atoms (white) or moieties responsible for largely negative electrostatic potential (red and blue). 97

Chapter 5: Dietary Vitamin A Decreases Liver Metastases of Colon Cancer in Mice ABSTRACT Previously, we showed that retinol inhibited all-trans-retinoic acid (ATRA)- resistant human colon cancer cell invasion via a retinoic acid receptor-independent mechanism in vitro. The objectives of the current study were to determine if dietary retinol inhibited metastasis of ATRA-resistant colon cancer cells in a nude mouse xenograft model. HCT-116, ATRA-resistant human colon cancer cells, were intrasplenically injected into female nude mice (BALB/cAnNCr-nu/nu). Injection of tumor cells resulted in the establishment of a splenic tumor which then shed cells that metastasized to the liver. Supplemental dietary vitamin A as retinyl palmitate was provided after injection for 5 wks in the chemotherapy study and for one month prior to and 5 wks after injection for the chemoprevention study. Consumption of a diet containing 200,000 IU vitamin A /kg diet decreased tumor incidence in the chemotherapy study and tumor multiplicity in the chemoprevention study. Supplementation with 200,000 IU vitamin A/kg diet decreased tumor incidence to 45.2% (P = 0.14) and tumor multiplicity to 17% (P = 0.03) of control in the chemotherapy and chemoprevention studies, respectively. Thus, supplemental dietary vitamin A may be an effective chemotherapeutic and chemopreventive agent to decrease the hepatic metastasis of colon cancer. 98

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