Repositorio
Institucional

Gidekel, Manuel

Malvicini, Mariana#Gutierrez-Moraga, Ana#Rodriguez, Marcelo M.#Gomez-Bustillo, Sofia#Salazar, Lorena#Sunkel, Carlos#Nozal, Leonor#Salgado, Antonio#Hidalgo, Manuel#Lopez-Casas, Pedro P.#Luis Novella, Jose#Jose Vaquero, Juan#Alvarez-Builla, Julio#Mora, Adda#Mazzolini, Guillermo

A Tricin Derivative from Deschampsia antarctica Desv. Inhibits Colorectal Carcinoma Growth and Liver Metastasis through the Induction of a Specific Immune Response

AMER ASSOC CANCER RESEARCH

MOLECULAR CANCER THERAPEUTICS

en

In colorectal carcinoma patients, distant metastatic disease is present at initial diagnosis in nearly 25% of them. The majority of patients with metastatic colorectal carcinoma have incurable disease, therefore, new therapies are needed. Agents derived from medicinal plants have already demonstrated therapeutic activities in human cancer cells. Antartina is an antitumor agent isolated from Deschampsia antarctica Desv. This study aimed to evaluate the antitumor properties of Antartina in colorectal carcinoma models. We used human and murine colorectal carcinoma cell lines for investigating proliferation, apoptosis, and cell-cycle effects of Antartina therapy in vitro. Avatar and immunocompetent colorectal carcinoma animal models were applied for evaluating the effects of Antartina in vivo. Immune response against colorectal carcinoma model was investigated using CTL assay, analyzing dendritic cell activation and intratumor T-cell subpopulation, and by tumor rechallenge experiments. Antartina inhibits in vitro human colorectal carcinoma cell proliferation, however, in vivo experiments in Avatar colorectal carcinoma model Antartina display a limited antitumor effect. In an immunocompetent colorectal carcinoma mice model, Antartina potently inhibited tumor growth andliver metastases, leading to complete tumorregressions in > 30% of mice and increased animal survival. In addition, Antartina induced a potent specific cytotoxic T-cell response against colorectal carcinoma and a long-lasting antitumor immunity. Interestingly, Antartina increased tumor immunogenicity and stimulated dendritic cell activation. No toxic effects were observed at the doses employed. Our findings showed that Antartina has the ability to induce antitumorimmunity against colorectal carcinoma and can be used to develop newtools for the treatment of colorectal carcinoma. (C) 2018 AACR.

Artículo original

We want to acknowledge Guillermo Gaston, Santiago Cabrera, and Franco Puebla for their support at our Animal Facilities. This work was supported by Uxmal and INNOVA Chile (grants 12IDL2-13648 and 15ITE2-49635, to M. Gidekel) and Universidad Austral 2016 (M. Malvicini).

Agradecemos a Guillermo Gastón, Santiago Cabrera y Franco Puebla por su apoyo en nuestro Bioterio. Este trabajo contó con el apoyo de Uxmal e INNOVA Chile (subvenciones 12IDL2-13648 y 15ITE2-49635, otorgadas a M. Gidekel) y de la Universidad Austral 2016 (M. Malvicini).

10.1158/1535-7163.MCT-17-0193

pdf

http://dx.doi.org/10.1158/1535-7163.MCT-17-0193

Oncology

Oncología

Inmunología

Farmacología y Farmacia

version publicada

dorada

acceso abierto

acceso abierto

WOS:000431314700008

A Tricin Derivative from <i>Deschampsia antarctica</i> Desv. Inhibits Colorectal Carcinoma Growth and Liver Metastasis through the Induction of a Specific Immune Response

Artículo original

AMER ASSOC CANCER RESEARCH

MOLECULAR CANCER THERAPEUTICS

Oncología

1535-7163

en

INNOVA 12IDL2-13648#INNOVA 15ITE2-49635

Uxmal

INNOVA Chile 12IDL2-13648

INNOVA Chile 15ITE2-49635

We want to acknowledge Guillermo Gaston, Santiago Cabrera, and Franco Puebla for their support at our Animal Facilities. This work was supported by Uxmal and INNOVA Chile (grants 12IDL2-13648 and 15ITE2-49635, to M. Gidekel) and Universidad Austral 2016 (M. Malvicini).

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