title: Inhibition of in vitro growth and arrest in the G0/G1 phase of HCT8 line human colon cancer cells by kaempferide triglycoside from Dianthus caryophyllus.
abstract: The effects of phytoestrogens have been studied in the hypothalamic-pituitary-gonadal axis and in various non-gonadal targets. Epidemiologic and experimental evidence indicates a protective effect of phytoestrogens also in colorectal cancer. The mechanism through which estrogenic molecules control colorectal cancer tumorigenesis could possibly involve estrogen receptor beta, the predominantly expressed estrogen receptor subtype in colon mucosa.To validate this hypothesis, we therefore used an engineered human colon cancer cell line induced to overexpress estrogen receptor beta, beside its native cell line, expressing very low levels of ERbeta and not expressing ERalpha; as a phytoestrogenic molecule, we used kaempferide triglycoside, a glycosylated flavonol from a Dianthus caryophyllus cultivar. The inhibitory properties of this molecule toward vegetal cell growth have been previously demonstrated: however, no data on its activity on animal cell or information about the mechanism of this activity are available. Kaempferide triglycoside proved to inhibit the proliferation of native and estrogen receptor beta overexpressing colon cancer cells through a mechanism not mediated by ligand binding dependent estrogen receptor activation. It affected HCT8 cell cycle progression by increasing the G(0)/G(1) cell fraction and in estrogen receptor beta overexpressing cells increased two antioxidant enzymes. Interestingly, the biological effects of this kaempferide triglycoside were strengthened by the presence of high levels of estrogen receptor beta.Pleiotropic molecular effects of phytoestrogens may explain their protective activity against colorectal cancer and may represent an interesting area for future investigation with potential clinical applications.
authors.affiliation: School of Medicine, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Martineti
authors.forename: Isabella
authors.initials: I
authors.lastname: Tognarini
authors.forename: Chiara
authors.initials: C
authors.lastname: Azzari
authors.forename: Silvia
authors.initials: S
authors.lastname: Carbonell Sala
authors.forename: Francesca
authors.initials: F
authors.lastname: Clematis
authors.forename: Marcello
authors.initials: M
authors.lastname: Dolci
authors.forename: Virginia
authors.initials: V
authors.lastname: Lanzotti
authors.forename: Francesco
authors.initials: F
authors.lastname: Tonelli
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Brandi
authors.forename: Paolo
authors.initials: P
authors.lastname: Curir
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D029749:Dianthus / Q000737:chemistry*; D047629:Estrogen Receptor beta / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D006027:Glycosides / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D044949:Kaempferols / Q000494:pharmacology* / Q000627:therapeutic use; D008517:Phytotherapy; D016192:Resting Phase, Cell Cycle / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D047629:Estrogen Receptor beta; D006027:Glycosides; D044949:Kaempferols; C449720:kaempferide