genistin and Neoplasms

Genistein, the principal soy isoflavone, is a molecule of great interest as an innovative chemotherapeutic agent or as a lead-compound in anticancer drug design. To enhance intrinsic activity of genistein and to explore its pharmacophoric potential, its glycosidic derivatives were synthesized. On the basis of structural features and calculated lipophilicity coefficient (ClogP) the derivatives were classified as hydrophilic (i.e. those containing free sugar moiety) or lipophilic (i.e. those with alkylated or acylated sugar hydroxyls). The in vitro cytostatic and cytotoxic studies showed hydrophilic glycosides to be practically inactive against human cancer cell lines when compared to the free aglycone. On the contrary, lipophilic glycosides were significantly more active than the parent isoflavone although the correlation between ClogP and the activity was not clear. On the basis of GI50 and LC50 values two of the most active glycosides were found to be several times more potent in their cytostatic and cytotoxic effect than genistein. Additionally all lipophilic glycosides were revealed to exhibit different mode of action in comparison to genistein. It may suggest that these compounds do not undergo rapid biodegradation, either in culture media or inside cells, and exert their biological effects primarily as intact molecules.

Topics: Anticarcinogenic Agents; Antineoplastic Agents, Phytogenic; Cell Division; Genistein; Glycosides; Humans; Isoflavones; Neoplasms; Soybean Proteins; Tumor Cells, Cultured

Cancer-protective effects of isoflavones like genistin or genistein are well known. High intakes and an adequate absorption rate of isoflavones are necessary for efficient chemoprevention, though other dietary agents might increase absorption efficacy. The aim of this study was to investigate the effect of phloridzin, an inhibitor of the sodium-dependent glucose transporter (SGLT1), on genistin absorption and metabolism.. Phloridzin and genistin were luminally administered in an isolated preparation of luminally and vascularly perfused rat small intestine. A synthetic perfusate free from blood components was used as vascular medium, with a perfluorocarbon as oxygen carrier. Luminal media consisted of a bicarbonate buffered sodium chloride solution spiked with genistin (24.5 micromol/l) and phloridzin (1 mmol/l).. In previous experiments, genistin absorption rate of 17.2% has been observed. In the present study, phloridzin administered simultaneously with genistin, increased genistin uptake 2.5 fold (44.5%).. The naturally occurring substance phloridzin, present in apples, thus considerably amplify genistin absorption. These effects might offer a promising novel method in designing functional foods for cancer prevention by combining genistin- and phloridzin-containing foods.

Topics: Animals; Food, Organic; Intestinal Absorption; Intestine, Small; Isoflavones; Male; Neoplasms; Phlorhizin; Rats; Rats, Sprague-Dawley