The Inhibitory Effect of Ellagic Acid on Cell Growth of Ovarian Carcinoma Cells

Abstract

Ellagic acid (EA) is able to inhibit the growth of several cancer cells; however, its effect on human ovarian carcinoma cells has not yet been investigated. Ovarian carcinoma ES-2 and PA-1 cells were treated with EA (10~100 μM) and assessed for viability, cell cycle, apoptosis, anoikis, autophagy, and chemosensitivity to doxorubicin and their molecular mechanisms. EA inhibited cell proliferation in a dose- and time-dependent manner by arresting both cell lines at the G1 phase of the cell cycle, which were from elevating p53 and Cip1/p21 and decreasing cyclin D1 and E levels. EA also induced caspase-3-mediated apoptosis by increasing the Bax : Bcl-2 ratio and restored anoikis in both cell lines. The enhancement of apoptosis and/or inhibition of autophagy in these cells by EA assisted the chemotherapy efficacy. The results indicated that EA is a potential novel chemoprevention and treatment assistant agent for human ovarian carcinoma.

Potential new chemotherapy strategy for human ovarian carcinoma with a novel KSP inhibitor

“…Mitotic arrest can cause the accumulation of P53 [29], and in particular P53 phosphorylated at serine 15 has been reported to induce apoptosis partly via activation of Bax [30]. While P53 expression was increased by carboplatin, KPYB10602 caused little increase of P53 in the present study (data not shown).…”

Ellagic acid: Pharmacological activities and molecular mechanisms involved in liver protection

“…EA exerts its beneficial effects by regulating multiple pathways including: (i) activation of the antioxidant response through the nuclear erythroid 2-related factor 2 (Nrf2) [73,74]; (ii) inhibition of proinflammatory agents, such as cyclooxygenase (COX-2) and cytokines by nuclear factor-kappa B (NF-B) [51,75]; (iii) alteration of several growth factors expression, as the platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-␤), hepatic growth factor (HGF) [76,77]; (iv) depletion of adhesion molecules, like vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) among others [78]; (v) modulation of several cell survival/cell-cycle genes such as cyclin D1 and E, p21, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) [79,80], tumor suppressors (p53, DUSP6, Fos), oncogenes (K-Ras, c-Myc) [81]; (vi) regulation of kinases, like mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3-K), glycogen synthase kinase 3 beta (GSK-3␤) [82][83][84] (Fig. 2).…”

“…In this respect, EA has shown chemopreventive effects in rodent models of oral [105,289,290], esophagic [291,292], mammary [293,294], lung [295], prostatic [296], intestinal [297] and colon cancer [298,299]. Besides, the antiproliferative activity of both EA and urolithins on several tumor cell lines has been clearly demonstrated Table 3 [79,[300][301][302][303]. In contrast, the evidence of anti-hepatocarcinogenic effects of EA is still contradictory (Table 3).…”

Polyphenol compounds and PKC signaling

“…For the most part, in nature, they exist as complexes called ellagitannins, which usually undergo hydrolysis in the gastrointestinal tract to form ellagic acid [178]. In vitro and in vivo studies have shown ellagic acid to exert antidiarrheal [179], anti-diabetic [180], anti-carcinogenic [181, 182], anti-inflammatory [183] properties.…”