Anticancer effects of wogonin in both estrogen receptor‐positive and ‐negative human breast cancer cell lines in vitro and in nude mice xenografts

Abstract

Wogonin is a plant monoflavonoid which has been reported to inhibit cell growth and/or induce apoptosis in various tumors. Herein, we investigated the in vitro and in vivo anticancer effects and associated mechanisms of wogonin in human breast cancer. Effects of wogonin were examined in estrogen receptor (ER)-positive and -negative human breast cancer cells in culture for proliferation, cell cycle progression, and apoptosis. The in vivo effect of oral wogonin was examined on tumor xenograft growth in athymic nude mice. The molecular changes associated with the biological effects of wogonin were analyzed by immunoblotting. Cell growth was attenuated by wogonin (50-200 lM), independently of its ER status, in a time-and concentration-dependent manner. Apoptosis was enhanced and accompanied by upregulation of PARP and Caspase 3 cleavages as well as proapoptotic Bax protein. Akt activity was suppressed and reduced phosphorylation of its substrates, GSK-3b and p27, was observed. Suppression of Cyclin D1 expression suggested the downregulation of the Akt-mediated canonical Wnt signaling pathway. ER expression was downregulated in ER-positive cells, while c-ErbB2 expression and its activity were suppressed in ER-negative SK-BR-3 cells. Wogonin feeding to mice showed inhibition of tumor growth of T47D and MDA-MB-231 xenografts by up to 88% without any toxicity after 4 weeks of treatment. As wogonin was effective both in vitro and in vivo, our novel findings open the possibility of wogonin as an effective therapeutic and/or chemopreventive agent against both ERpositive and -negative breast cancers, particularly against the more aggressive and hormonal therapy-resistant ER-negative types. ' 2007 Wiley-Liss, Inc.

Wogonin Induces Apoptosis by Activation of ERK and p38 MAPKs Signaling Pathways and Generation of Reactive Oxygen Species in Human Breast Cancer Cells

“…Consequently, nitric oxide synthesis and prostaglandin E2 production are inhibited Kim et al, 2001). In addition, it has been reported that wogonin posesses anticancer activities in several cancer cells, including myelogenous leukemia cells , hepatomacellular carcinoma cells (Wang et al, 2006a), breast cancer cells (Chung et al, 2008), murine sacrcoma S 180 cells (Wang et al, 2006b) and bladder cancer cells (Ikemoto et al, 2000). Interestingly, wogonin has no effect on inducing apoptosis in PBMCs and fibroblasts (Liu et al, 2002).…”

Combination of wogonin and sorafenib effectively kills human hepatocellular carcinoma cells through apoptosis potentiation and autophagy inhibition

“…Wogonin has been shown to have antioxidant, antiviral, antithrombotic and anti-inflammatory activities in both in vitro and in vivo studies (26)(27)(28)(29). The anticancer activity of wogonin is demonstrated by inducing apoptosis in cancer cells and suppressing growth of human cancer xenografts in vivo (30,31). Wogonin has also been tested to kill cancer cells in combination with other chemotherapeutics (32,33).…”

Wogonin triggers apoptosis in human osteosarcoma U-2 OS cells through the endoplasmic reticulum stress, mitochondrial dysfunction and caspase-3-dependent signaling pathways

“…Wogonin (5,7-dihydroxy-8-methoxyflavone, C 16 H 12 O 5 ) is one of the active ingredients extracted from the roots of Scutellaria baicalensis Georgi. It has been reported that wogonin induced apoptosis in many tumor cells such as human breast cancer cell lines (8), prostate cancer cells (10), hepatocellular carcinoma SK-HEP-1 cells (11), promyeloleukemic cells (10) cancer A2780 cells (12) and it suppressed tumor cells growth (13).…”

“…Flavonoids, one of the most common active ingredients of medicinal herbs, possess pharmacological properties including anti-infammatory (5,6), antioxidant (7), and antitumor (8,9) activities. Wogonin (5,7-dihydroxy-8-methoxyflavone, C 16 H 12 O 5 ) is one of the active ingredients extracted from the roots of Scutellaria baicalensis Georgi.…”