Arctiin induces cell growth inhibition through the down-regulation of cyclin D1 expression.
Arctiin is a major lignan constituent of Arctium lappa and has anti-cancer properties in animal models. It was recently reported that arctiin induces growth inhibition in human prostate cancer PC-3 cells. However, the growth inhibitory mechanism of arctiin remains unknown. Herein we report that arctiin induces growth inhibition and dephosphorylates the tumor-suppressor retinoblastoma protein in human immortalized keratinocyte HaCaT cells. We also show that the growth inhibition caused by arctiin is associated with the down-regulation of cyclin D1 protein expression. Furthermore, the arctiin-induced suppression of cyclin D1 protein expression occurs in various types of human tumor cells, including osteosarcoma, lung, colorectal, cervical and breast cancer, melanoma, transformed renal cells and prostate cancer. Depletion of the cyclin D1 protein using small interfering RNA-rendered human breast cancer MCF-7 cells insensitive to the growth inhibitory effects of arctiin, implicates cyclin D1 as an important target of arctiin. Taken together, these results suggest that arctiin down-regulates cyclin D1 protein expression and that this at least partially contributes to the anti-proliferative effect of arctiin.
Matsuzaki
Youichirou
Y
Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Koyama
Makoto
M
Hitomi
Toshiaki
T
Yokota
Tomoya
T
Kawanaka
Mayumi
M
Nishikawa
Akiyoshi
A
Germain
Doris
D
Sakai
Toshiyuki
T
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism*; D015536:Down-Regulation; D005663:Furans / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D005960:Glucosides; D016160:Retinoblastoma Protein; D019938:Cyclin D1; C077992:arctiin