ANTICANCER PROPERITES AND MDR MODULATORY EFFECT OF PLANT POLYPHENOLS AND THEIR INTERACTION WITH MEMBRANE COMPONENTS

• Published in: Anticancer research Vol. 28; no. 5C
• Main Authors: Michalak, K, Wesolowska, O, Wisniewski, J, Sroda, K, Teisseyre, A, Kuzdzal, M, Strancar, J, Duarte, N, Ferreira, M-JU
• Format: Journal Article
• Language: English
• Published: 01-10-2008
• ISSN: 0250-7005

Many compounds of plant origin have been identified to be interesting for potential application in cancer prevention or chemotherapy. Such agents were found among flavonoids and stilbenes. In broad in vitro and in vivo studies, the ability of plant-derived polyphenols to interact with different cellular targets was revealed. Resveratrol (trans-3,4,5'-trihydro-xystilbene) influences many cellular signaling pathways and affects all three stages of carcinogenesis. In this work the effect of several stilbenes (resveratrol, its analogue piceatannol, and piceatannol derivatives) and some flavonoids on activity of ABC multidrug transporters and potassium channels Kv1.3 was examined. Recently the role of potassium channel activity in cancer has emerged. Several of the compounds studied were found to be potent potassium channel inhibitors. Strong inhibition of membrane transporters and ion channels was often observed for hydroxy-, methoxy-, acetoxy-and prenyl- derivatives in relation to the parent compounds. Piceatannol, naringenin and some of their derivatives were the most active inhibitors of MRP1 multidrug transporter. The influence of plant polyphenols on integral membrane proteins such as MDR transporters and ion channels can be mediated at least in part by non-specific membrane effects. Flavonoids and stilbene interactions with lipid bilayers was determined by fluorescence and ESR spectroscopy. Simulation of the experimental ESR spectra and application of GHOST condensation method were applied to study the effect of polyphenols on membrane domain structure. The significance of interaction of studied phytochemicals with membrane transporters, channels and lipid bilayer for their anticancer properties was discussed. Antiproliferative properties of the compounds were tested in sensitive and doxorubicin-resistant, P-gp overexpressing colon cancer cell lines LoVo and LoVo/Dx, respectively. Tangeretin, natural polymethoxylated flavone and 8-prenylnaringenin most effectively inhibited cell growth both in sensitive and resistant cancer cell lines. Antiproliferative action was compared with pro-apoptic properties of the compounds.