Protective effect of methanol extract of latex of Calotropis procera in an experimental model of colorectal cancer

Abstract

Ethnopharmacological relevanceThe plant, Calotropis procera, has been used for treating various gastrointestinal disorders and cancer. Some of these medicinal properties have been attributed to the latex produced by the plant. Aim of the studyTo evaluate the efficacy of methanol extract of air-dried latex (MeDL) of C. procera in the rat model of colorectal cancer (CRC). Materials and methodsCRC was induced in the rats by 1,2-dimethylhydrazine (DMH) and the effect of MeDL was evaluated at two doses (50 and 150 mg/kg). MeDL and reference drug aspirin (60 mg/kg) were administered orally starting from 1 h before injecting DMH till 8 weeks after the second dose of DMH. The study also included experimental and normal control groups. Microscopic analysis was carried out to determine the count for aberrant crypt foci (ACF) and histology score whereas enzyme-linked immunosorbent assay and immunohistochemical analyses were performed for markers of carcinogenesis and angiogenesis. Other parameters that were evaluated include deoxyribonucleic acid (DNA) fragmentation, laddering, Bcl2 and Bax immunoreactivity, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity. ResultsSubcutaneous injection of DMH induced pre-neoplastic changes in the colon of rats with the appearance of ACF with multiple crypts (1–3, 4–6 or >6). In the experimental control group, total ACF count was 3.49 ± 0.23/cm of the colon length and the median histology score was 2.0 for architectural abnormalities, 2.0 for dilatation of crypts and 1.5 for hyperplasia/dysplasia against 1.0 for all the characteristics in normal rats. Oral administration of MeDL similar to aspirin, led to a reduction in ACF count and histology score of CRC concomitant with a decrease in the levels of markers of carcinogenesis - β-catenin and proliferating cell nuclear antigen (PCNA); markers of angiogenesis - matrix metallopeptidase-9 (MMP-9) and vascular endothelial growth factor (VEGF), and an increase in apoptotic DNA fragmentation. ConclusionMeDL confers protection in the rat model of CRC and the study suggests its therapeutic potential in this condition.