Membrane-rigidifying effects of anti-cancer dietary factors

Article type: Research Article

Authors: Tsuchiya, Hironori | Nagayama, Motohiko | Tanaka, Toshiyuki | Furusawa, Miyuki | Kashimata, Masanori | Takeuchi, Hiroshi

Affiliations: Department of Dental Pharmacology, Asahi University School of Dentistry, Hozumi, Gifu 501-0296, Japan | Department of Oral Pathology, Asahi University School of Dentistry, Hozumi, Gifu 501-0296, Japan | Gifu Prefectural Institute of Health and Environmental Sciences, Naka, Kakamigahara 504-0838, Japan

Note: [] Address for correspondence: Hironori Tsuchiya, Ph.D., Department of Dental Pharmacology, Asahi University School of Dentistry, 1851 Hozumi, Hozumi-cho, Motosu-gun, Gifu 501-0296, Japan. Tel.: +81 58 329 1432; Fax: +81 58 329 1432; E-mail: hiro@dent.asahi-u.ac.jp

Abstract: Since several anti-cancer drugs interact with cell membrane lipids, the effects of anti-cancer dietary factors on liposomal membranes with different lipid composition were comparatively studied by measuring fluorescence polarization. Fluidity was imparted on both hydrophobic and hydrophilic regions of lipid bilayers by decreasing cholesterol and increasing unsaturated phosphatidylcholine in membranes. At 0.625–10 μM, (–)-epigallocatechin gallate, genistein, apigenin, resveratrol and a reference anti-cancer drug, doxorubicin, rigidified the tumor cell model membranes consisting of 20 mol% cholesterol and 80 mol% phosphatidylcholine with the acyl chain 18:1/16:0 ratio of 1.0, but not daidzein. They were more effective on the membrane core than the membrane surface. Quercetin showed a biphasic effect on the hydrophobic regions of membrane lipid bilayers to rigidify above 5 μM and fluidize below 2.5 μM. In contrast, anti-cancer dietary factors and doxorubicin were not or much less effective in rigidifying the normal cell model membranes consisting of 40 mol% cholesterol and 60 mol% phosphatidylcholine with the acyl chain 18:1/16:0 ratio of 0.5. The membrane-rigidifying effects were greater depending on a decrease of the cholesterol/phosphatidylcholine ratio and an increase of the phosphatidylcholine unsaturation degree. Membrane-active dietary factors and doxorubicin inhibited the growth of mouse myeloma cells at 10–100 μM, while the growth inhibition by membrane-inactive daidzein was relatively weak. Anti-cancer dietary factors appear to act on more fluid membranes like tumor cells as well as doxorubicin to induce rigidification, especially in the hydrocarbon core of membrane lipids, which is determined by the composition of cholesterol and unsaturated phospholipids.

Keywords: anti-cancer dietary factor, liposomal membrane, fluidity, membrane-rigidifying effect, lipid composition

Journal: BioFactors, vol. 16, no. 3-4, pp. 45-56, 2002