Anticancer activity of flavonol and flavan-3-ol rich extracts from Croton celtidifolius latex

摘要

Context: Croton celtidifolius Baill (Euphorbiaceae) is a tree found in the Atlantic Forest in Southern Brazil, where it is commonly known as "Sangue-de-Dragao". Its red latex is used traditionally for treating ulcers, diabetes and cancer.Objective: To evaluate antitumor activities of Croton celtififolius latex in vitro and in vivo. Material and methods: Phytochemical analyses were conducted using HPLC-DAD-MS. Cytotoxic, nuclease and pro-apoptotic properties were determined using the tetrazolium salt assay (MTT), plasmid DNA damage assay and ethidium bromide (EB)/acridine orange methods, respectively, and antitumor activity was determined in the Ehrlich ascites carcinoma (EAC) mouse model. Results: Phytochemical studies indicated a high phenol content of flavonols (45.67 ±0.24 and 18.01 ±0.23mg/mL of myricetin and quercetin, respectively) and flavan-3-ols (114.12 ±1.84 and 1527.41 ±16.42 mg/L of epicatechin and epigallocatechin, respectively) in latex. These compounds reduced MCF-7 and EAC cell viability in the MTT assay (IC_(50) = 169.0 ±1.8 and 187.0 ± 2.2 mug/mL, respectively). Latex compounds caused significant DNA fragmentation and increased the number of apoptotic cells (negative control (NC), 12%; latex, 41%) as indicated by differential staining in the EB/acridine orange assay. The in vivo latex treatment at 3.12mg/kg/day reduced the body weight by 7.57 ± 2.04 g and increased median survival time to 17.5 days when compared to the NC group (13.0 days). In addition, the highest latex concentration inhibited tumor growth by 56%.Discussion and conclusion: These results agree with ethno-pharmacological reports showing cytotoxicity and antitumor activity of C. celtidifofius latex. The mechanism of antitumor action may be related to,direct DNA fragmentation that reduces survival and induces apoptosis.