Paullinia cupana Mart var. sorbilis, guaraná, reduces cell proliferation and increases apoptosis of B16/F10 melanoma lung metastases in mice

Abstract

We showed that guaraná (Paullinia cupana Mart var. sorbilis) had a chemopreventive effect on mouse hepatocarcinogenesis and reduced diethylnitrosamine-induced DNA damage. In the present experiment, we evaluated the effects of guaraná in an experimental metastasis model. Cultured B16/F10 melanoma cells (5 x 10 5 cells/animal) were injected into the tail vein of mice on the 7th day of guaraná treatment (2.0 mg P. cupana/g body weight, per gavage) and the animals were treated with guaraná daily up to 14 days until euthanasia (total treatment time: 21 days). Lung sections were obtained for morphometric analysis, apoptotic bodies were counted to calculate the apoptotic index and proliferating cell nuclear antigen-positive cells were counted to determine the proliferation index. Guaraná-treated (GUA) animals presented a 68.6% reduction in tumor burden area compared to control (CO) animals which were not treated with guaraná (CO: 0.84 ± 0.26, N = 6; GUA: 0.27 ± 0.24, N = 6; P = 0.0043), a 57.9% reduction in tumor proliferation index (CO: 23.75 ± 20.54, N = 6; GUA: 9.99 ± 3.93, N = 6; P = 0.026) and a 4.85-fold increase in apoptotic index (CO: 66.95 ± 22.95, N = 6; GUA: 324.37 ± 266.74 AB/mm 2 , N = 6; P = 0.0152). In this mouse model, guaraná treatment decreased proliferation and increased apoptosis of tumor cells, consequently reducing the tumor burden area. We are currently investigating the molecular pathways of the effects of guaraná in cultured melanoma cells, regarding principally the cell cycle inhibitors and cyclins.

Effect of Paullinia cupana on MCF-7 breast cancer cell response to chemotherapeutic drugs

“…Other studies have also described the antitumor activity of guarana using animal and cell experimental models (32)(33)(34). It has been suggested that guarana may be used to improve CRF caused by chemotherapy, which prompted us to conduct the present study.…”

Paullinia cupana Kunth (Sapindaceae): A review of its ethnopharmacology, phytochemistry and pharmacology

“…Low toxicity Vermaak (2011), Mello (2010a, , Santa Maria (1998), Mattei (1998), andFonseca (1994) Antioxidant activity Bittencourt (2013), Portella (2013), Dalonso (2012), Majhenic (2007), Mendes and Carlini (2007), Yamaguti-Sasaki (2007), Basile (2005), and Mattei (1998) Antibacterial and antifungal activities Basile (2013Basile ( , 2005, Majhenic (2007), Yamaguti-Sasaki (2007) Antidepressive, anxiolytic and antiamnesic effects Roncon (2011), Shahwar (2010, Antonelli (2007), Majhenic (2007), Otobone (2005Otobone ( , 2007, , Basile (2005), Espinola (1997), and Mattei (1998) Chemoprophylactic in carcinogenesis and antigenotoxic activity Fukumasu (2011Fukumasu ( , 2008Fukumasu ( , 2006a, Oliveira ( , 2011, Leite (2011);Cragg (2006), and Espinola (1997) Inhibition of platelet aggregation Bydlowski (1991Bydlowski ( , 1988) Protection against gastric lesions Campos (2003) Lower risk of obesity, hypertension and metabolic syndrome Krewer (2011) Antifatigue effects Campos (2011) The seeds of Guaraná also contain acylglycerols and cyanolipids (Figure 3), an unusual class of plant lipids restricted to only a few families, such as Sapindaceae, Hippocastanacaeae and Boraginaceae (Moller and Seigler, 1999). The study of the oil from P. cupana Kunth var.…”

“…Guaraná seeds have been investigated for their potential effect as a chemoprophylactic in carcinogenesis and antigenotoxic activity in vivo (Fukumasu et al, 2011(Fukumasu et al, , 2008(Fukumasu et al, , 2006a(Fukumasu et al, , 2006bOliveira et al, 2011Oliveira et al, , 2002Leite et al, 2011;Cragg et al, 2006;Espinola et al, 1997), such as the inhibition of platelet aggregation in vitro and in vivo (Bydlowski et al, 1991(Bydlowski et al, , 1988, protection against gastric lesions induced by ethanol and indomethacin in vivo (Campos et al, 2003) and the treatment of inflammatory allergic diseases (Jippo et al, 2009). An in vivo study to investigate the association between habitual Guaraná ingestion and the prevalence of metabolic disease exhibited a possible protective effect against obesity, hypertension and metabolic syndrome, all of which are related to a higher risk of cardiovascular disease (Krewer et al, 2011).…”

“…Tel: +55 21 3204 2094. (Fukumasu et al, 2008). It is also an ingredient in some soft drinks, non-alcoholic beverages and cosmetics.…”

Paullinia cupana Mart. var. sorbilis, guarana, increases survival of Ehrlich ascites carcinoma (EAC) bearing mice by decreasing cyclin‐D1 expression and inducing a G0/G1 cell cycle arrest in EAC cells

“…sorbilis, also known as guarana, belongs to the Sapindaceae family. Currently under investigation in our laboratory in cancer models as a chemopreventive or chemotherapeutic agent, Paullinia cupana is so far showing interesting results (Fukumasu et al, 2008(Fukumasu et al, , 2006.…”