RESUMEN
The research for innovative treatments against colon adenocarcinomas is still a great challenge. Acacia catechu Willd. heartwood extract (AC) has health-promoting qualities, especially at the gastrointestinal level. This study characterized AC for its catechins content and investigated the apoptosis-enhancing effect in human colorectal adenocarcinoma HT-29 cells, along with its ability to spare healthy tissue. MTT assay was used to describe the time course, concentration dependence and reversibility of AC-mediated cytotoxicity. Cell cycle analysis and AV-PI and DAPI-staining were performed to evaluate apoptosis, together with ROS formation, mitochondrial membrane potential (MMP) changes and caspase activities. Rat ileum and colon rings were tested for their viability and functionality to explore AC effects on healthy tissue. Quantitative analysis highlighted that AC was rich in (±)-catechin (31.5 ± 0.82 mg/g) and (-)-epicatechin (12.5 ± 0.42 mg/g). AC irreversibly decreased cell viability in a concentration-dependent, but not time-dependent fashion. Cytotoxicity was accompanied by increases in apoptotic cells and ROS, a reduction in MMP and increases in caspase-9 and 3 activities. AC did not affect rat ileum and colon rings' viability and functionality, suggesting a safe profile toward healthy tissue. The present findings outline the potential of AC for colon cancer treatment.
Asunto(s)
Acacia/química , Apoptosis/efectos de los fármacos , Catequina/farmacología , Extractos Vegetales/farmacología , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Animales , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Relación Dosis-Respuesta a Droga , Células HT29 , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Acacia catechu Willd. is a plant diffused in India and other Asian countries, where it is used as a traditional medicine for the treatment of several ailments including diarrhea, one of the most common pathologies worldwide. In this study, we determined the chemical composition of Acacia catechu Willd. extract (AC) and evaluated its effect on spontaneous and induced contractility in isolated guinea pig ileum and proximal colon. Preliminary data about its antimicrobial effect against some pathogen agents versus some microbiota intestinal strain have been also reported. Chemical analysis revealed the presence of catechins, such as (-)-Epicatechin and (+)-Catechin. AC extract reduced frequency and amplitude of colon smooth muscle spontaneous contractility, in a concentration-dependent manner. A weaker effect of the extract was exerted toward ileum smooth muscle spontaneous contractility. The observed calcium antagonistic effect was more potent in proximal colon than in ileum. The extract showed a noncompetitive reversible antagonism to carbachol, both in proximal colon and ileum, with a higher potency in proximal colon. The antimicrobial effects of AC extract were observed toward Campylobacter jejuni, Escherichia coli, and Salmonella spp., while Bifido and Lactobacillus were not affected by treatment. These effects, however, occurred at concentrations fivefold higher than those inhibiting ileum and colon contractility. In conclusion, our results suggest that AC affects intestinal contractility without affecting intestinal bacterial flora and this may result in clinical benefits in patients suffering from nonbacterial diarrhea.