Sesamin, a lignan of sesame, down-regulates cyclin D1 protein expression in human tumor cells.
Sesamin is a major lignan constituent of sesame and possesses multiple functions such as antihypertensive, cholesterol-lowering, lipid-lowering and anticancer activities. Several groups have previously reported that sesamin induces growth inhibition in human cancer cells. However, the nature of this growth inhibitory mechanism remains unknown. The authors here report that sesamin induces growth arrest at the G1 phase in cell cycle progression in the human breast cancer cell line MCF-7. Furthermore, sesamin dephosphorylates tumor-suppressor retinoblastoma protein (RB). It is also shown that inhibition of MCF-7 cell proliferation by sesamin is correlated with down-regulated cyclin D1 protein expression, a proto-oncogene that is overexpressed in many human cancer cells. It was found that sesamin-induced down-regulation of cyclin D1 was inhibited by proteasome inhibitors, suggesting that sesamin suppresses cyclin D1 protein expression by promoting proteasome degradation of cyclin D1 protein. Sesamin down-regulates cyclin D1 protein expression in various kinds of human tumor cells, including lung cancer, transformed renal cells, immortalized keratinocyte, melanoma and osteosarcoma. Furthermore, depletion of cyclin D1 protein using small interfering RNA rendered MCF-7 cells insensitive to the growth inhibitory effects of sesamin, implicating that cyclin D1 is at least partially related to the antiproliferative effects of sesamin. Taken together, these results suggest that the ability of sesamin to down-regulate cyclin D1 protein expression through the activation of proteasome degradation could be one of the mechanisms of the antiproliferative activity of this agent.
Yokota
Tomoya
T
Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Matsuzaki
Youichirou
Y
Koyama
Makoto
M
Hitomi
Toshiaki
T
Kawanaka
Mayumi
M
Enoki-Konishi
Masako
M
Okuyama
Yusuke
Y
Takayasu
Junko
J
Nishino
Hoyoku
H
Nishikawa
Akiyoshi
A
Osawa
Toshihiko
T
Sakai
Toshiyuki
T
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056741:Cyclin D; D016213:Cyclins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D004149:Dioxoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D016193:G1 Phase / Q000187:drug effects; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006801:Humans; D017705:Lignans / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011480:Protease Inhibitors / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D061988:Proteasome Inhibitors; D000090063:Proto-Oncogene Mas; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D012715:Sesame Oil / Q000494:pharmacology*
D056741:Cyclin D; D016213:Cyclins; D004149:Dioxoles; D006131:Growth Inhibitors; D017705:Lignans; C000715470:MAS1 protein, human; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D000090063:Proto-Oncogene Mas; D016160:Retinoblastoma Protein; D012715:Sesame Oil; D046988:Proteasome Endopeptidase Complex; C054125:sesamin