title: Cytotoxic activity of nemorosone in human MCF-7 breast cancer cells.
abstract: Estrogen receptor (ER) antagonists have been widely used for breast cancer treatment; however, patients have increasingly shown resistance and sensitivity to the high toxicity of these drugs, and identification of novel targeted therapies is therefore required. To determine whether nemorosone, a polycyclic polyisoprenylated benzophenone isolated from floral resins of Clusia rosea Jacq. and Cuban propolis samples, exerts anticancer effects on human breast cancer cells, estrogen receptor positive (ERα+) MCF-7 and estrogen receptor negative (ERα-) MDA-MB-231 and LNCaP cells were used. Cells were treated with nemorosone alone or in association with 17β-estradiol (E2) or an ER antagonist, ICI 182,780, a selective ER downregulator that completely abrogates estrogen-sensitive gene transcription. Nemorosone inhibited the cell viability of ERα+ but not of ERα- cells. In MCF-7, nemorosone induced inhibition of cell growth by blocking the cell cycle in the G₀/G₁ phase. Moreover, the expression of pERK1/2 and pAkt, considered to be hallmarks of the nongenomic estrogen signalling pathway, were reduced in MCF-7 cells treated with nemorosone. All these effects were enhanced by ICI 182,780. However, nemorosone was not able to interfere with E2-induced Ca²(+) release. These findings suggest that nemorosone may have therapeutic application in the treatment of breast cancer because of its activity on ERα.
authors.affiliation: Department of Pharmaceutical Sciences, University of Salerno, Fisciano, Italy. apopolo@unisa.it
authors.forename: Ada
authors.initials: A
authors.lastname: Popolo
authors.forename: Anna Lisa
authors.initials: AL
authors.lastname: Piccinelli
authors.forename: Silvana
authors.initials: S
authors.lastname: Morello
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Sorrentino
authors.forename: Cuesta Rubio
authors.initials: CR
authors.lastname: Osmany
authors.forename: Luca
authors.initials: L
authors.lastname: Rastrelli
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinto
authors.forename: Pinto
authors.initials: P
authors.lastname: Aldo
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000627:therapeutic use / Q000633:toxicity*; D001577:Benzophenones / Q000302:isolation & purification / Q000627:therapeutic use / Q000633:toxicity*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D031251:Clusia; D003603:Cytotoxins / Q000302:isolation & purification / Q000627:therapeutic use / Q000633:toxicity*; D005260:Female; D006801:Humans; D010936:Plant Extracts / Q000302:isolation & purification / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001577:Benzophenones; D003603:Cytotoxins; D010936:Plant Extracts; C437463:nemorosone