title: Estrogenic activity of osthole and imperatorin in MCF-7 cells and their osteoblastic effects in Saos-2 cells.
abstract: There is an increasing interest in phytoestrogens due to their potential medical usage in hormone replacement therapy (HRT). The present study was designed to investigate the in vitro effects of estrogen-like activities of two widespread coumarins, osthole and imperatorin, using the MCF-7 cell proliferation assay and their alkaline phosphatase (ALP) activities in osteoblasts Saos-2 cells. The two compounds were found to strongly stimulate the proliferation of MCF-7 cells. The estrogen receptor-regulated ERα, progesterone receptor (PR) and PS2 mRNA levels were increased by treatment with osthole and imperatorin. All these effects were significantly inhibited by the specific estrogen receptor antagonist ICI182, 780. Cell cycle analysis revealed that their proliferation stimulatory effect was associated with a marked increase in the number of MCF-7 cells in S phase, which was similar to that observed with estradiol. It was also observed that they significantly increased ALP activity, which was reversed by ICI182,780. These results suggested that osthole and imperatorin could stimulate osteoblastic activity by displaying estrogenic properties or through the ER pathway. In conclusion, osthole and imperatorin may represent new pharmacological tools for the treatment of osteoporosis.
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Xin
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Hou
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Nai-Dai
authors.initials: ND
authors.lastname: Zhang
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Xu
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: zqy1965@163.com.
authors.forename: Qiao-Yan
authors.initials: QY
authors.lastname: Zhang
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: qinsmmu@126.com.
authors.forename: Lu-Ping
authors.initials: LP
authors.lastname: Qin
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D031048:Cnidium / Q000737:chemistry*; D003374:Coumarins / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D011564:Furocoumarins / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D048789:Phytoestrogens / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism
chemical_list: D003374:Coumarins; D004365:Drugs, Chinese Herbal; D011564:Furocoumarins; D048789:Phytoestrogens; D011960:Receptors, Estrogen; D000469:Alkaline Phosphatase; C031534:imperatorin; C046627:osthol
keywords: Alkaline phosphatase; Estrogen receptors; Estrogenic activity; Imperatorin; MCF-7; Osteoblasts; Osthole