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

Context: Croton celtidifolius Baill (Euphorbiaceae) is a tree found in the Atlantic Forest in Southern Brazil where it is commonly known as “Sangue-de-Dragão”. 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, nucleasic, and pro-apoptotic properties were determined using the tetrazolium salt assay (MTT), plasmid DNA damage assay, and ethidium bromide/acridine orange methods, respectively, and antitumor activity was determined in the Erlich ascites carcinoma (EAC) mouse model. Results: Phytochemical studies indicated a high phenol content of flavonols (45.67 ± 0.24 and 18.01 ± 0.23 mg/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 (IC50 = 169.0 ± 1.8, and 187.0 ± 2.2 mg/mL, respectively). Latex compounds caused significant DNA fragmentation and increased numbers of apoptotic cells (Negative control, 12%; latex, 41%) as indicated by differential staining in the ethidium bromide/acridine orange assay. The in vivo latex treatment at 3.12 mg/kg/day reduced body weight by 7.57 ± 2.04 g and increased median survival time to 17.5 days when compared to the negative control group (13.0 days). In addition, the highest latex concentration inhibited tumor growth by 56%. Discussion and conclusion: These results agree with ethno-pharmacological 24 reports showing cytotoxicity and antitumor activity of C. celtidifolius latex. The mechanism of antitumor action may be related to direct DNA fragmentation that reduces survival and induces apoptosis.