Ethanolic Extract of Bark from Salix aegyptiaca Ameliorates 1,2-dimethylhydrazine-induced Colon Carcinogenesis in Mice by Reducing Oxidative Stress.
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.
a Faculté des Sciences Biologiques, Laboratoire de Biologie Cellulaire et Moléculaire, Université des Sciences et de la Technologie Houari Boumediene , Bab-Ezzouar , Algiers , Algeria.
Abdelkader
A
Bounaama
b Middle East Technical University , Department of Biology , Ankara , Turkey.
Shabnam
S
Enayat
b Middle East Technical University , Department of Biology , Ankara , Turkey.
Muserref Seyma
MS
Ceyhan
a Faculté des Sciences Biologiques, Laboratoire de Biologie Cellulaire et Moléculaire, Université des Sciences et de la Technologie Houari Boumediene , Bab-Ezzouar , Algiers , Algeria.
Hichem
H
Moulahoum
a Faculté des Sciences Biologiques, Laboratoire de Biologie Cellulaire et Moléculaire, Université des Sciences et de la Technologie Houari Boumediene , Bab-Ezzouar , Algiers , Algeria.
Bahia
B
Djerdjouri
b Middle East Technical University , Department of Biology , Ankara , Turkey.
Sreeparna
S
Banerjee
D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D058739:Aberrant Crypt Foci / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000431:Ethanol / Q000737:chemistry; D045325:HCT116 Cells / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D032108:Salix / Q000737:chemistry*
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D010936:Plant Extracts; D000431:Ethanol; D019813:1,2-Dimethylhydrazine