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.

Biscaro, F.; Parisotto, E.; Citadini Zanette, V.; Günther, T.M.; Ferreira, E.; Gris, E.; Correia, J.F.; Pich, C.; Mattivi, F.; Filho, D.; Pedrosa, R. (2013). Anticancer activity of flavonol and flavan-3-ol rich extracts from Croton celtidifolius latex. PHARMACEUTICAL BIOLOGY, 51 (6): 737-743. doi: 10.3109/13880209.2013.764331 handle: http://hdl.handle.net/10449/21910

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

Mattivi, Fulvio;
2013-01-01

Abstract

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.
Sangue-de-Dragão
DNA fragmentation
Apoptosis
Cytotoxicity
Antitumor
Settore CHIM/08 - CHIMICA FARMACEUTICA
2013
Biscaro, F.; Parisotto, E.; Citadini Zanette, V.; Günther, T.M.; Ferreira, E.; Gris, E.; Correia, J.F.; Pich, C.; Mattivi, F.; Filho, D.; Pedrosa, R. (2013). Anticancer activity of flavonol and flavan-3-ol rich extracts from Croton celtidifolius latex. PHARMACEUTICAL BIOLOGY, 51 (6): 737-743. doi: 10.3109/13880209.2013.764331 handle: http://hdl.handle.net/10449/21910
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