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

被引:14
作者
Piloto-Ferrer, Janet [1 ]
Sanchez-Lamar, Angel [2 ]
Francisco, Marbelis [1 ]
Gonzalez, Maria L. [1 ]
Merino, Nelson [3 ]
Aparicio, Guillermo [3 ]
Perez, Carlos [4 ]
Rodeiro, Idania [5 ]
Paz Lopes, Miriam Teresa [6 ]
机构
[1] Ctr Invest & Desarrollo Medicamentos CIDEM, Dept Toxicol Genet & Antitumorales, Ave 26,1605 E Puentes Grandes & Boyeros, Havana, Cuba
[2] Univ La Habana, Dept Biol Vegetal, Lab Toxicol Genet, Fac Biol, Calle 25,455 E I&J, Havana, Cuba
[3] Ctr Invest & Desarrollo Medicamentos CIDEM, Dept Toxicol & Farmacol, Ave 26,1605 E Puentes Grandes & Boyeros, Havana, Cuba
[4] UCMH, Dept Bioquim, Inst Ciencias Basicas & Preclin Victoria de Giron, Calle 146 3102, Havana, Cuba
[5] Inst Ciencias Mar ICIMAR, Dept Farmacol, Loma 14,Plaza Revoluc, Havana, Cuba
[6] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Farmacol, Avda Antonio Carlos 6627, Belo Horizonte, MG, Brazil
关键词
Anti-metastatic; Anti-mitotic; Anti-proliferative; Colon cancer; Xanthatins; Xanthium strumarium; BIOLOGICAL-ACTIVITY; COLORECTAL-CANCER; CYCLE ARREST; IN-VITRO; INHIBITION; CHECKPOINT; GROWTH; L; PROLIFERATION; ANGIOGENESIS;
D O I
10.1016/j.phymed.2018.12.019
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
Background: 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. Hypothesis/Aim: 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. Study design: 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. Results: Our in vitro results show that X. strumarium, mediated by xanthatins, induces G(2)/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. Conclusion: 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.
引用
收藏
页码:236 / 244
页数:9
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