Anticarcinogenic Effects of the Ethanolic Extract ofSalix aegyptiacain Colon Cancer Cells: Involvement of Akt/PKB and MAPK Pathways

Abstract

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.].

<p>TRIM14 promotes cell proliferation and inhibits apoptosis by suppressing PTEN in colorectal cancer</p>

“…18 The blockage of the AKT pathway possesses anti-tumorigenic effects in CRC cells and provides a potential strategy for CRC treatment. [32][33][34] As a negative regulator of the AKT pathway, PTEN is downregulated in CRC 20 and serves as a tumor suppressor in CRC. 21 Herein, consistent with earlier findings, TRIM14 overexpression increased p-AKT levels and decreased PTEN levels in CRC cells ( Figure 5).…”

miR-218 inhibits the invasion and migration of colon cancer cells by targeting the PI3K/Akt/mTOR signaling pathway

“…The involvement of this pathway in the development of colon cancer and metastasis, including cell proliferation, apoptosis and migration, has been extensively investigated (15)(16)(17)(18). Furthermore, the blockade of PI3K/Akt activity in colon cancer cells has shown promising anti-cancer effects (19)(20)(21)(22). Recent studies have demonstrated that the downstream factor of the PI3K/Akt pathway, the mammalian target of rapamycin (mTOR), is a potential therapeutic target in various types of cancer, including non-small cell lung cancer (23) (26), non-Hodgkin's lymphoma (27) and leukemia (28,29).…”

Antioxidant and Anti-Inflammatory Activities of Salix Aegyptiaca Bark Extract Attribute to Its Anticancer Efficacy

“…9 . Some recent reports showed anticancer activity of bark extract of S. aegyptiaca against human colon cancer cell lines and mouse model 10,11,12 .…”

“…The underlying mechanisms related to anticancer efficacy of S. aegyptiaca bark extract are yet to be explored, however some studies showed that the inhibition of colon cancer cells proliferation was mediated through G1/S cell cycle arrest and induction of apoptosis through p53 dependent pathway. Other pathways include the inhibition of PI3K/Akt and MAP Kinase pathways, and inhibition of epithelial to mesenchymal transition with the treatment of S. aegyptiaca bark extract 11,12 . Ethanolic extract of S. aegyptiaca bark exhibited chemopreventive efficacy against 1,2-dimethylhydrazine induced colon carcinogenesis in mice through antioxidant and antiinflammatory activities 10 .…”