Anti-proliferative effect of horehound leaf and wild cherry bark extracts on human colorectal cancer cells

Abstract

Marubium vulgare (horehound) and Prunus serotina (wild cherry) have been traditionally used for the treatment of inflammatory-related symptoms such as cold, fever, and sore throat. In this report, we show that extracts of anti-inflammatory horehound leaves and wild cherry bark exhibit antiproliferative activity in human colorectal cancer cells. Both horehound and wild cherry extracts cause suppression of cell growth as well as induction of apoptosis. We found that horehound extract upregulates pro-apoptotic non-steroidal anti-inflammatory drug-activated gene (NAG-1) through transactivation of the NAG-1 promoter. In contrast, wild cherry extract decreased cyclin D1 expression and increased NAG-1 expression in HCT-116 and SW480 cell lines. Treatment with wild cherry extract resulted in the suppression of β-catenin/T cell factor transcription, as assessed by TOP/FOP reporter constructs, suggesting that suppressed β-catenin signaling by wild cherry extract leads to the reduction of cyclin D1 expression. Our data suggest the mechanisms by which these extracts suppress cell growth and induce apoptosis involve enhanced NAG-1 expression and/or downregulation of β-catenin signaling, followed by reduced cyclin D1 expression in human colorectal cancer cells. These findings may provide mechanisms for traditional anti-inflammatory products as cancer chemopreventive agents.

Antiproliferative Activity of Marrubium persicum Extract in the MCF-7 Human Breast Cancer Cell Line

“…Our findings provided insight into a new implication of the traditional usage of M. persicum found in Armenia, Azarbaijan, Turkey and Iran as a potential novel cancer chemopreventive agent, where incorporation of this plant in herbal remedy may help prevent or reduce the risk of breast cancer and other oxidative stress associated diseases. Several studies in this filed have shown that genus Marrubium is of potential value for detecting antiproliferative agents, as Yamaguchi et al determined the anti-inflammatory and antiproliferative activity of M. vulgare leaves in human colorectal cancer cells via suppression of cell growth as well as induction of apoptosis (Yamaguchi et al, 2006). Elsewhere, diterpenoids from M. cylleneum and M. velutinum were evaluated for their cytotoxic effects against various cancer cell line and immunomodulating potential in human peripheral blood mononuclear cells in vitro assays by Karioti et al, revealing strong tumor regression in a broad range of tumor cells (Karioti et al, 2007).…”

Molecular characterisation of canine nonsteroidal anti-inflammatory drug-activated gene (NAG-1)

“…NAG-1 is up-regulated by a number of anti-tumorigenic compounds in addition to NSAIDs, including peroxisome proliferator-activated receptor γ (PPARγ) ligands (Baek et al, 2003;2004b;Yamaguchi et al, 2006a), phosphatidylinositol 3-kinase inhibitor (Yamaguchi et al, 2004) and chemopreventive dietary compounds, such as resveratrol (Baek et al, 2002a), indole-3-carbinol , conjugated linoleic acid (Lee et al, 2006) and epicatechin gallate (Baek et al, 2004a), as well as anti-inflammatory plant extracts (Yamaguchi et al, 2006b). Interestingly, induction of NAG-1 by these compounds occurs by multiple mechanisms at the levels of transcription and post-transcription.…”

A novel peroxisome proliferator–activated receptor γ ligand, MCC-555, induces apoptosis via posttranscriptional regulation of NAG-1 in colorectal cancer cells

“…However, NAG-1 has been shown to possess antitumorigenic and proapoptotic activity in some types of cancer cells (19,22,23). NAG-1 is up-regulated in several epithelial cancer cell lines by several nonsteroidal anti-inflammatory drugs (23), as well as by antitumorigenic compounds such as resveratrol (24), catechins (25), indole-3 carbinol (26), conjugated linoleic acid (27), PPARg ligands (13), DIM derivatives (28), horehound extracts (29), and 5F-203 (30). In contrast to other transforming growth factor-h superfamily genes, NAG-1 contains a p53 binding site in the 5 ¶ upstream region (19,22,23), and several dietary compounds induce NAG-1 expression via p53 (24,25).…”