Phenolic esters from the rhizomes of Cimicifuga racemosa do not cause proliferation effects in MCF-7 cells

Five phenylpropanoid esters, caffeoylglycolic acid, 2-caffeoylpiscidic acid (cimicifugic acid D), 3,4-dihydroxyphenacyl caffeate (petasiphenone), 3,4-dihydroxyphenyl-2-oxopropyl isoferulate (cimiciphenol) and 3,4-dihydroxyphenacyl isoferulate (cimiciphenone) were isolated from a commercially available extract of the rhizomes of Cimicifuga racemosa (L.) Nutt. (syn. Actaea racemosa L.) for the first time; the known cimicifugic acids A, B, E, F, fukinolic acid, fukiic acid and caffeic acid were also obtained. Cimiciphenone and caffeoylglycolic acid are new natural products. The structures were elucidated by means of spectroscopic data (ESI-MS, 1H-, 13C-NMR, COSY, HMQC, HMBC and NOE experiments). Ferulic acid and isoferulic acid were detected by HPLC analysis in comparison to standards. The estrogenic activity of the isolated compounds was tested in an estrogen-dependent MCF-7 mamma carcinoma cell line; 17beta-estradiol (10(-11) M) and the phytoestrogen coumestrol (10(-7) - 10(-5) M) were used as references. The results suggest that, in contrast to an earlier report, the phenolic esters do not exert a proliferative (estrogenic) effect in this test system.     

Petasiphenone, a phenol isolated from Cimicifuga racemosa, in vitro inhibits proliferation of the human prostate cancer cell line LNCaP

Extracts of Cimicifuga racemosa (L.) Nutt. (syn.: Actaea racemosa L.) (CR) inhibit the proliferation of the human prostate cancer cell line LNCaP. Recently, the phenylpropanoid ester 3,4-dihydroxyphenacyl caffeate (petasiphenone, 1) was isolated from CR. This substance is a structural homologue to petasiphenol ([3-(3,4-dihydroxyphenyl)-2-oxopropyl caffeate]), a compound produced by Petasites japonicus Sieb. & Zucc. which inhibits the growth of various human leukemia cell lines. Because of the structural similarity, we examined whether 1 affects the proliferation of LNCaP cells and the secretion of prostate-specific antigen (PSA). Under basal conditions as well as under co-incubation with 10 nM estradiol [E2 or 1 nM dihydrotestosterone (DHT)], 1 dose-dependently inhibited proliferation of LNCaP cells while PSA release per cell was not altered. We report for the first time that a defined compound isolated from CR inhibits the growth of the human prostate cancer cells LNCaP.