Antiproliferative effects of new dimeric ellagitannins from Cornus alba in prostate cancer cells

Abstract

Prostate tumors can be categorized as benign prostate hyperplasia (BPH), which is an overgrowth of the prostate caused by extensive androgen-dependent tissue remodeling [1], and prostate cancer (PCa), which is a malignant tumor caused by oncogenic mutations, aberrant signaling or inflammatory conditions [2]. On the worldwide scale, PCa, as second in the estimated new cases and fifth in the estimated deaths in males, is one of the most prevalent cancers [3]. Cornus alba Linne (CA, Cornaceae), which is known as red-barked, white or Siberian dogwood, is native to Siberia, northern China and Korea [4] and the Cornus species have been also used as an East Asian folk remedy for urinary health and natural tonic in aging men [5]. Various phytochemicals including terpenoid and flavonoid have been isolated from these species [6 – 7]. Activity-guided isolation of 80% acetone extract of CA yielded one novel compound, tentatively designated cornusiin H (13, molecular formula; C75H56O48), together with 12 known phenolic compounds including four flavonoids [catechin (1), quercetin-3-O-β-D-glucuronide (2), quercetin-3-O-β-D-glucopyranoside (3), kaempferol-3-O-β-D-glucopyranoside (4)] and eight hydrolysable tannins [gallic acid (5), 2,6-di-O-galloyl-hamamelofuranoside (6), 2-galloyl-4-caffeoyl-L-threonic acid (7) 2,3-di-O-galloyl-4-caffeoyl-L-threonic acid (8), 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranoside (9), cornusiin B (10), cornusiin A (11) and camptothin B (12)]. The antiproliferative effects of the isolated compounds have been assessed in hormone-dependent prostate cancer cell, LNCaP. The dimeric ellagitannins (11-13) selectively inhibited the proliferation of LNCaP. And flow cytometry analysis results indicated that the dimeric ellagitannins (11-13) induced apoptosis and S-phase arrest of LNCaP. These results suggest that the dimeric ellagitannins from CA can be developed as functional materials or herbal medicines for prostate tumor such as early-stage prostate cancer.