Xanthium strumarium´s xanthatins induces mitotic arrest and apoptosis in CT26WT colon carcinoma cells

• Published in: Phytomedicine (Stuttgart) Vol. 57; pp. 236 - 244
• Main Authors: Piloto-Ferrer, Janet, Sánchez-Lamar, Ángel, Francisco, Marbelis, González, Maria L., Merino, Nelsón, Aparicio, Guillermo, Pérez, Carlos, Rodeiro, Idania, Lopes, Miriam Teresa Paz
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.04.2019
• Subjects: Animals; Anti-metastatic; Anti-mitotic; Anti-proliferative; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Colon cancer; Colonic Neoplasms - drug therapy; Colonic Neoplasms - pathology; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; Drug Screening Assays, Antitumor; Furans - pharmacology; Male; Mice, Inbred BALB C; Mitosis - drug effects; Plant Extracts - chemistry; Plant Extracts - pharmacology; Xanthatins; Xanthium - chemistry; Xanthium strumarium; WEXs; Anti-proliferative; CEXs; Colon cancer; Anti-mitotic; Xanthatins; SAC; Anti-metastatic; Chk1; Chk2; XF; Xanthium strumarium
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2018.12.019

Colorectal cancer is one of the most common malignancies worldwide and is associated with high mortality rates. We previously reported that Xanthium strumarium L. induces mitotic arrest in proliferating cells, a process mediated by xanthatins. The aim of this work is to study if xanthatins, isolated from X. strumarium total extract, affect the proliferative capacity of CT26WT colon cancer cells and, in consequence, if tumor growth and proliferation of (lung) metastatic sites can also be arrested in vivo. This study consisted of both in vitro and in vivo experiments involving the CT26WT cell line and a subcutaneous mouse model of colon cancer. In vitro cell cycle progression, in vivo tumoral growth and anti-metastatic activity were analyzed to investigate whether xanthatins of X. strumarium induce mitotic arrest in proliferating colorectal carcinoma. Our in vitro results show that X. strumarium, mediated by xanthatins, induces G2/M arrest and impair anaphase entrance. This leads to a significant induction of apoptotic and necrotic in CT26WT cells, demonstrating their significant anti-proliferative activity through interfering with the mitotic apparatus. Furthermore, our in vivoresults reveal that X. strumarium inhibits both tumor growth and metastasis progression. X. strumarium antitumor activities are mainly mediated by xanthatins through inhibition of tumor growth and metastasis, inducing mitotic arrest and apoptosis in colon carcinoma cells. These findings further confirm the therapeutic potential of X. strumarium in colorectal cancer. [Display omitted]