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: Ada Popolo, Anna Lisa Piccinelli, Silvana Morello, Rosalinda Sorrentino, Cuesta Rubio Osmany, Luca Rastrelli, Aldo Pinto, Pinto Aldo
• Journal: Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 89 Issue 1 Pg. 50-7 (Jan 2011) ISSN: 1205-7541 [Electronic] Canada
• PMID: 21186377 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Benzophenones
• Cytotoxins
• Plant Extracts
• nemorosone

Topics

• Antineoplastic Agents, Phytogenic (isolation & purification, therapeutic use, toxicity)
• Benzophenones (isolation & purification, therapeutic use, toxicity)
• Breast Neoplasms (drug therapy, pathology)
• Calcium Signaling (drug effects, physiology)
• Cell Line, Tumor
• Cell Survival (drug effects, physiology)
• Clusia
• Cytotoxins (isolation & purification, therapeutic use, toxicity)
• Female
• Humans
• Plant Extracts (isolation & purification, therapeutic use, toxicity)