"A tricin derivative from Deschampsia antarctica Desv. inhibits colorectal carcinoma growth and liver metastasis through the induction of a specific immune response"

MORA, ADDA; NOVELLA, JOSE LUIS; SALGADO, ANTONIO; SALAZAR, LORENA; GUTIERREZ-MORAGA, ANA; GIDEKEL, MANUEL; VAQUERO, JUAN JOSE; HIDALGO, MANUEL; SUNKEL, CARLOS; RODRIGUEZ, MARCELO M.; MAZZOLINI, GUILLERMO; ALVAREZ-BUILLA, JULIO; LOPEZ-CASAS, PEDRO P.; NOZAL, LEONOR; GOMEZ-BUSTILLO, SOFIA; MALVICINI, MARIANA

MOLECULAR CANCER THERAPEUTICS

AMER ASSOC CANCER RESEARCH

Año: 2018

1535-7163

In colorectal carcinoma (CRC) patients, distant metastatic disease is present at initial diagnosis in nearly 25% of them. The majority of patients with metastatic CRC 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 CRC models. We used human and murine CRC cell lines for investigating proliferation, apoptosis and cell cycle effects of Antartina? therapy in vitro. Avatar and immunocompetent CRC animal models were applied for evaluating the effects of Antartina? in vivo. Immune response against CRC model was investigated using CTL assay, analyzing dendritic cell activation and intratumor T cell sub-population, and by tumor rechallenge experiments. Antartina? inhibits in vitro human CRC cell proliferation; however, in vivo experiments in Avatar CRC model Antartina? display a limited antitumor effect. In an immunocompetent CRC mice model Antartina? potently inhibited tumor growth and liver metastases, leading to complete tumor regressions in >30% of mice and increased animal survival. In addition, Antartina? induced a potent specific cytotoxic T cell response against CRC, 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 antitumor immunity against CRC and can be used to develop new tools for the treatment of CRC.