Cytotoxic activity of nemorosone in human MCF-7 breast cancer cells.
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.
Department of Pharmaceutical Sciences, University of Salerno, Fisciano, Italy. firstname.lastname@example.org, , , , , ,
MeSHAntineoplastic Agents, Phytogenic
Cell Line, Tumor
Pub Type(s)Comparative Study
Research Support, Non-U.S. Gov't