Chemoprevention of tumor metastasis by liposomal beta-sitosterol intake.
To investigate chemopreventive effect of liposomal beta-sitosterol on tumor metastasis, we prepared liposomal beta-sitosterol composed of egg yolk phosphatidylcholine for oral delivery. Although orally administered beta-sitosterol (4 micromol as beta-sitosterol/mouse) was not absorbed into plasma, the amount of immune response cytokines such as IL-12 and IL-18 was increased in the small intestine after the liposome intake. Moreover, after daily oral administration of the liposome for 7 d, natural killer (NK) cell activity in the mice was increased, suggesting that the immune surveillance activity of mice was enhanced by the liposomal beta-sitosterol intake. Thus, we examined metastatic potential of B16BL6 melanoma cells, which were intravenously injected into mice after sequential administration of liposomal beta-sitosterol for 7 d. The number of metastatic colonies in the lungs was significantly less than that of control group two weeks after the injections of the cells. These results suggest that daily liposomal beta-sitosterol intake prevents tumor metastasis may be due to enhancement of gut immune surveillance systems.
Imanaka
Hiromichi
H
Department of Medical Biochemistry, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Koide
Hiroyuki
H
Shimizu
Kosuke
K
Asai
Tomohiro
T
Kinouchi Shimizu
Naomi
N
Ishikado
Atsushi
A
Makino
Taketoshi
T
Oku
Naoto
N
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008081:Liposomes; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary / Q000648:ultrastructure; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D012855:Sitosterols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D020382:Interleukin-18; D008081:Liposomes; D012855:Sitosterols; D018664:Interleukin-12; C025473:gamma-sitosterol