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Modeling Colitis-Associated Cancer with Azoxymethane AOM and Dextran Sulfate Sodium DSS
Published on: September 11, 2012
Laherradurin Inhibits Tumor Growth in an Azoxymethane/Dextran Sulfate Sodium Colorectal Cancer Model In Vivo
Michael Joshue Rendón-Barrón1,2, Eduardo Pérez-Arteaga1, Izamary Delgado-Waldo1
1Unidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran, Av. Vasco de Quiroga 15, Col. Belisario Domínguez Sección XVI, Tlalpan, Ciudad de México 14080, Mexico.
Abstract:
Colorectal cancer (CRC) is the third most common neoplasia in the world. Its mortality rate is high due to the lack of specific and effective treatments, metastasis, and resistance to chemotherapy, among other factors. The natural products in cancer are a primary source of bioactive molecules. In this research, we evaluated the antitumor activity of an acetogenin (ACG), laherradurin (LH), isolated from the Mexican medicinal plant Annona macroprophyllata Donn.Sm. in a CRC murine model. The CRC was induced by azoxymethane-dextran sulfate sodium (AOM/DSS) in Balb/c mice and treated for 21 days with LH or cisplatin. This study shows for the first time the antitumor activity of LH in an AOM/DSS CRC model. The acetogenin diminished the number and size of tumors compared with cisplatin; the histologic studies revealed a recovery of the colon tissue, and the blood toxicity data pointed to less damage in animals treated with LH. The TUNEL assay indicated cell death by apoptosis, and the in vitro studies exhibited that LH inhibited cell migration in HCT116 cells. Our study provides strong evidence of a possible anticancer agent for CRC.
Insights
Laherradurin, a natural compound from *Annona macroprophyllata*, shows significant antitumor effects against colorectal cancer (CRC) in mice. This compound reduced tumor size and promoted colon tissue recovery with less toxicity than cisplatin.
Area of Science:
- Natural product chemistry
- Oncology
- Pharmacology
Background:
- Colorectal cancer (CRC) presents a significant global health challenge with high mortality rates due to limited treatment options, metastasis, and chemoresistance.
- Natural products are a vital source of novel bioactive molecules for cancer therapy.
- Acetogenins (ACGs) are a class of compounds with demonstrated anticancer potential.
Purpose of the Study:
- To evaluate the antitumor activity of laherradurin (LH), an acetogenin isolated from *Annona macroprophyllata*, in a preclinical model of colorectal cancer.
- To compare the efficacy and toxicity of LH with cisplatin, a standard chemotherapy drug.
Main Methods:
- Colorectal cancer was induced in Balb/c mice using the azoxymethane-dextran sulfate sodium (AOM/DSS) model.
- Mice were treated for 21 days with either LH or cisplatin.
- Tumor burden, histological changes, blood toxicity, apoptosis (TUNEL assay), and in vitro cell migration were assessed.
Main Results:
- Laherradurin (LH) demonstrated significant antitumor activity, reducing both the number and size of colorectal tumors compared to cisplatin.
- Histological examination revealed recovery of colon tissue architecture in LH-treated mice.
- Blood toxicity analysis indicated less systemic damage in animals treated with LH compared to cisplatin.
- TUNEL assays confirmed induction of apoptosis (programmed cell death) by LH.
- In vitro studies showed that LH inhibited cell migration in HCT116 colorectal cancer cells.
Conclusions:
- Laherradurin exhibits potent antitumor effects in a preclinical colorectal cancer model.
- LH demonstrates a favorable safety profile with reduced toxicity compared to cisplatin.
- LH warrants further investigation as a potential therapeutic agent for colorectal cancer.
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