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Modeling Colitis-Associated Cancer with Azoxymethane AOM and Dextran Sulfate Sodium DSS
Published on: September 11, 2012
Chemopreventive Effects of Onosma mutabilis against Azoxymethane-Induced Colon Cancer in Rats via Amendment of
Ahmed Aj Jabbar1, Ibrahim Abdel Aziz Ibrahim2, Fuad O Abdullah3,4
1Department of Medical Laboratory Technology, Erbil Technical Health and Medical College, Erbil Polytechnic University, Erbil 44001, Iraq.
Abstract:
Onosma species (Boraginaceae) are well known as medicinal plants due to their wide range of pharmaceutical potential. The present study aims to investigate the anticancer (in vitro) and chemo-protective (in vivo) efficacies of Onosma mutabilis extract (OME) in the azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rats. The in vitro antiproliferative effects of OME were determined on two human tumor cell lines (Caco-2 and HT-29) via MTT assay. The in vivo chemoprotective effects of OME were investigated by performing various biochemical analyses in serum and tissue homogenates of albino rats, along with determining oxidative stress biomarkers. Inflammatory biomarkers of colon, colonic gross morphology (by methylene blue), ACF formation, and colonic histopathology (H & E stain) were determined. The immunohistochemistry of colonic tissues was also assessed by Bax and Bcl-2 protein expression. The results showed that the antitumor activity of OME against Caco-2 and HT-29 colorectal cancer cells ranged between 22.28-36.55 µg/mL. OME supplementation caused a significant drop in the ACF values and improved the immunohistochemistry of the rats shown by up-regulation of Bax and down-regulation of Bcl-2 protein expressions. These outcomes reveal that O. mutabilis may have chemoprotective efficiency against AOM-induced colon cancer represented by the attenuation of ACF formation possibly through inhibition of free radicals, inflammation, and stimulation of the colon antioxidant armory (SOD, CAT, and GPx) and positive regulation of the Nrf2-Keap1 pathway.
Insights
Onosma mutabilis extract shows anticancer effects against colon cancer cells in vitro. In vivo, it protects against azoxymethane-induced colon cancer in rats by reducing aberrant crypt foci and inflammation.
Area of Science:
- Pharmacology
- Cancer Biology
- Natural Products Chemistry
Background:
- Onosma species are recognized for their medicinal properties.
- Colorectal cancer remains a significant global health concern.
- Investigating natural compounds for cancer prevention is crucial.
Purpose of the Study:
- To evaluate the in vitro anticancer and in vivo chemoprotective effects of Onosma mutabilis extract (OME).
- To assess OME's efficacy against azoxymethane (AOM)-induced aberrant crypt foci (ACF) in a rat model.
Main Methods:
- In vitro antiproliferative activity against Caco-2 and HT-29 cells using MTT assay.
- In vivo studies involved biochemical analyses, oxidative stress and inflammatory biomarker assessment, ACF quantification, histopathology, and immunohistochemistry (Bax, Bcl-2).
Main Results:
- OME exhibited antitumor activity against colorectal cancer cell lines (22.28-36.55 µg/mL).
- OME supplementation significantly reduced ACF formation and modulated Bax/Bcl-2 protein expression in AOM-treated rats.
- OME improved antioxidant status (SOD, CAT, GPx) and potentially regulated the Nrf2-Keap1 pathway.
Conclusions:
- Onosma mutabilis extract demonstrates significant chemoprotective potential against AOM-induced colon cancer in rats.
- OME's efficacy may stem from its antioxidant, anti-inflammatory, and pro-apoptotic properties.
- Further research into O. mutabilis as a chemopreventive agent is warranted.
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