Reduction of Preneoplastic Lesions Induced by 1,2-Dimethylhydrazine in Rat Colon by Maslinic Acid, a Pentacyclic Triterpene from Olea europaea L.

Abstract

Maslinic acid triggers compelling antiproliferative and pro-apoptotic effects in different human cancer cell lines. Hence, the chemopreventive activity was investigated on early stages of carcinogenesis induced by 1,2-dimethylhydrazine (DMH) which is a model that mimics human sporadic colorectal cancer. Male Sprague-Dawley rats were orally administered either maslinic acid at 5, 10 or 25 mg/kg dissolved in (2-hydroxypropyl)-β-cyclodextrin 20% (w/v) or the solvent for 49 days. After one week of treatment, animals received three weekly intraperitoneal injections of DMH at the dose of 20 mg/kg. Maslinic acid reduced the preneoplastic biomarkers, aberrant crypt foci (ACF) and mucin-depleted foci (MDF), already at 5 mg/kg in a 15% and 27%, respectively. The decline was significant at 25 mg/kg with decreases of 33% and 51%, respectively. Correlation analysis showed a significant association between the concentrations of maslinic acid found in the colon and the reduction of ACF (r = 0.999, P = 0.019) and MDF (r = 0.997, P = 0.049). The present findings demonstrate that maslinic acid induced an inhibition of the initiation stages of carcinogenesis. The assessment of this pentacyclic triterpene at the colon sheds light for designing diets with foods rich in maslinic acid to exert a chemopreventive activity in colorectal cancer.

An Integrative Approach to Characterize the Early Phases of Dimethylhydrazine-Induced Colorectal Carcinogenesis in the Rat

“…This protocol was adapted from Zhu et al [ 10 ]. Once a week, for seven weeks, animals from both groups CRC received an intraperitoneal injection of DMH [ 13 ], at a dose of 40 mg/kg of body weight (BW) [ 14 ], prepared immediately before its use as described above. Animals from CTRL groups were intraperitoneally injected with the vehicle (1 mM EDTA-saline) ( Figure 1 ).…”

The Role of Cyclodextrins in the Design and Development of Triterpene-Based Therapeutic Agents

“…The inhibitory effect of MA on the aberrant crypt foci and mucin-depleted foci, two biomarkers synthesized in the early stages of colon cancer, was highlighted in a murine model in the presence of HP-β-CD, which increased MA solubility and bioavailability [ 144 ].…”

The Anticancer Potential of Maslinic Acid and Its Derivatives: A Review

“…In vivo, MA could reduce the content of preneoplastic biomarkers in 1,2-dimethylhydrazine -induced colon cancer rat models and 5 mg/kg MA could decrease aberrant crypt foci and mucin-depleted foci amount by 15% and 27%, respectively; when MA was 25 mg/kg, the amount decreased by 33% and 51%, respectively ( Table 1 ). 40 Further, the Apc Min/+ mouse model is widely used in the study of human chemotherapeutic agents because it can simulate human spontaneous intestinal tumorigenesis. A recent study showed that Apc Min/+ mice treated with 100 mg/kg MA for six weeks reduced the formation of total intestinal polyps by 45%.…”