The bark from Salix species of plants has been traditionally consumed for its antiinflammatory properties. Because inflammation frequently accompanies the progress of colorectal cancer (CRC), we have evaluated the anticancer properties of the ethanolic extract from the bark (EEB) of S. aegyptiaca, a Salix species endogenous to the Middle East, using HCT-116 and HT29 CRC cell lines. Fresh bark from S. aegyptiaca was extracted with ethanol, fractionated by solvent-solvent partitioning and the fractions were analyzed by tandem mass spectrometry. Catechin, catechol, and salicin were the most abundant constituents of the extract. Interestingly, EEB showed the highest anticancer effect in the colon cancer cells followed by its fractions in ethyl acetate and water, with catechin, catechol, and salicin showing the least efficacy. EEB could strongly reduce the proliferation of the cancer cells, but not of CCD-18Co, normal colon fibroblast cell line. Accompanying this was cell cycle arrest at G1/S independent of DNA damage in the cancer cells, induction of apoptosis through a p53 dependent pathway and an inhibition of PI3K/Akt and MAP Kinase pathways at levels comparable to known commercial inhibitors. We propose that the combination of the polyphenols and flavonoids in EEB contributes toward its potent anticarcinogenic effects. [Supplementary materials are available for this article. Go to the publisher's online edition of Nutrition and Cancer for the following free supplemental resource(s): Supplementary Figure 1 and Supplementary Figure 2.].
We have previously shown that ethanolic extract from bark (EEB) of Salix aegyptiaca (Musk Willow) can inhibit proliferation and motility and induce apoptosis in colon cancer cells. Tandem mass spectrometry revealed EEB to be rich in catechin, catechol, and salicin. The present study investigated the chemopreventive effect of HPLC-fingerprinted EEB on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) formation in mice. DMH (20 mg/kg body weight) was weekly injected subcutaneously to mice for the first 2 weeks. EEB (100 and 400 mg/kg body weight) was provided orally from the 7th to 14th week, after which colon tissues were evaluated histologically and biochemically. DMH treatment induced high number of ACF; EEB significantly reduced the number and multiplicity of ACF, along with a restoration in goblet cells and mucin accumulation. EEB supplementation improved the markers of inflammation (myeloperoxidase and neutrophil infiltration) and oxidative stress. More importantly, EEB amplified apoptosis of neoplastic cells in the colon mucosa of DMH-treated mice. It also lowered levels of markers for early transformation events such as EGFR, nuclear β-catenin, and COX-2 in colon cancer cell lines HT-29 and HCT-116. The innocuity of EEB (up to 1600 mg/kg) to mice reinforces its potential as a chemopreventive agent.
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