Yerba mate (Ilex paraguariensis) induces apoptosis in murine colon cáncer models; the intrinsic pathway as a possible mechanism.

GARCIA-LAZARO RS; LORENZO N; CALIGIURI LG; LAMDAN H; BERENGENO AL; ORTEGA HH; ALONSO DF ; FARINA HG

Mar del Plata

Congreso; reunión anual de la sociedad argentina de investigación clínica; 2020

SAIC

Colorectal cancer (CRC) is one of the so-called westernized diseasesand is the third most common cancer in both men and women.In a previous work, we reported that yerba mate extract (YMe) fromIlex paraguariensis, a native South American tree which has a largeamount of bioactive compounds, inhibits CT26 cell proliferation byinduction of apoptosis. The aim of this research was to determinethe mechanism by which apoptosis is induced by YMe. To this end,in vitro and in vivo experimentation was carried out using CRC models.The mechanism of cellular apoptosis has an initiation and an executionphase. The initiation phase has two possible origins: the extrinsicor intrinsic pathway. It is reported that a key point in the intrinsicpathway of cellular apoptosis are mitochondrial permeabilizationprocesses, which are regulated by members of the Bcl-2 proteinfamily. In vitro, we investigated the expression of the Bcl-2 proteinusing CT26 cells. Western blot analysis showed that the level ofanti-apoptotic protein Bcl-2 was decreased in YMe treated cells. Immunofluorescenceanalyses also revealed a similar result. In vivo,using a murine syngeneic tumor model, we showed that oral administrationof YMe significantly inhibited tumor growth. The tumorgrowth rate is the result of the balance between the proliferation andthe induction to apoptosis of the neoplastic cells. Therefore, to determinewhether this reduction in tumor growth was due to an increasein cell apoptosis, a TUNEL assay on the tumor section was performed.In agreement with what was observed in vitro, the TUNELassay demonstrated that consumption of YMe increased apoptosisin cells in tumor tissues. In vitro and in vivo results suggest that YMeinduces apoptosis by the intrinsic pathway; however, further studiesare needed to confirm this assumption.