Janet Piloto-Ferrer1, Ángel Sánchez-Lamar2, Marbelis Francisco3, Maria L González3, Nelsón Merino4, Guillermo Aparicio4, Carlos Pérez5, Idania Rodeiro6, Miriam Teresa Paz Lopes7. 1. Departamento de Toxicología Genética y antitumorales, Centro de Investigación y Desarrollo de Medicamentos (CIDEM), Avenida 26, No. 1605 e/ Puentes Grandes y Boyeros, La Habana, Cuba. Electronic address: janet.piloto@cidem.cu. 2. Departamento de Biología Vegetal, Laboratorio de Toxicología Genética, Facultad de Biología, Universidad de la Habana, Calle 25, No. 455, e/ I y J, Vedado, La Habana, Cuba. 3. Departamento de Toxicología Genética y antitumorales, Centro de Investigación y Desarrollo de Medicamentos (CIDEM), Avenida 26, No. 1605 e/ Puentes Grandes y Boyeros, La Habana, Cuba. 4. Departamento de Toxicología y Farmacología, Centro de Investigación y Desarrollo de Medicamentos (CIDEM), Avenida 26, No. 1605 e/ Puentes Grandes y Boyeros, La Habana, Cuba. 5. Departamento de Bioquímica, Instituto de Ciencias Básicas y Preclínicas "Victoria de Girón" (ICBP), Universidad de Ciencias Médicas de La Habana (UCMH). Calle 146 # 3102, Playa, La Habana, Cuba. 6. Departamento de Farmacología, Instituto de Ciencias del Mar (ICIMAR), Loma 14, Alturas del Vedado, Plaza de la Revolución, La Habana, Cuba. 7. Departamento de Farmacología, Instituto de Ciencias Biológicas (ICB) Universidad Federal de Minas Gerais (UFMG), Avda. Antonio Carlos 6627, Belo Horizonte, Minas Gerais, Brasil.
Abstract
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 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. 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.
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 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. 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.
Authors: Bao-Ai Han; Xiu-Ping Yang; Davood K Hosseini; Po Zhang; Ya Zhang; Jin-Tao Yu; Shan Chen; Fan Zhang; Tao Zhou; Hai-Ying Sun Journal: Sci Rep Date: 2020-06-16 Impact factor: 4.379