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Melatonin Sensitizes Human Colorectal Cancer Cells to γ-ray Ionizing Radiation In Vitro and In Vivo.
Int J Mol Sci. 2018 Dec 10; 19(12)IJ

Abstract

Colorectal cancer is the most commonly reported gastrointestinal malignancy, with a recent, rapid increase of the annual incidence all over the world. Enhancing the radiosensitivity of cancer cells while preserving the health of normal cells is one of the most important tasks in clinical radiobiology. However, resistance to radiotherapy for colorectal cancer greatly decreases the therapeutic outcome. Melatonin (N-acetyl-5-methoxytryptamine), a natural secretory product that the pineal gland in the brain normally produces, has been reported to have anticancer properties. In the study, we investigated the combination of melatonin with radiotherapy as a treatment for colorectal cancer. We firstly explored the anti-tumor activity of melatonin combined with ionizing radiation (IR) against colorectal carcinoma in vitro. It was found that melatonin effectively inhibited human colorectal carcinoma cell line HCT 116 cellular proliferation, colony formation rate and cell migration counts following IR. Increasing the radiosensitivity of colorectal cancer cells by melatonin treatment was found to be associated with cell cycle arrest in the G2/M phase, downregulation of proteins involved in DNA double-strand break repair and activation of the caspase-dependent apoptotic pathway. Moreover, we also investigated the combined effect of IR and melatonin on colorectal tumor in vivo. Results from a tumor xenograft showed that melatonin plus IR treatment significantly suppressed tumor cell growth compared with melatonin or IR alone, resulting in a much higher tumor inhibition rate for the combined treatment. The data suggested that melatonin combined with IR could improve the radiosensitivity of colorectal cancer and thus enhance the therapeutic effect of the patients, implying melatonin could function as a potential sensitizer in tumor radiotherapy.

Authors+Show Affiliations

Tianjin Key Lab of Radiation Medicine Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. wangqin@irm-cams.ac.cn.Tianjin Key Lab of Radiation Medicine Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. sunzj@irm-cams.ac.cn.Tianjin Key Lab of Radiation Medicine Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. dlq@irm-cams.ac.cn.Tianjin Key Lab of Radiation Medicine Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. xuchang@irm-cams.ac.cn.Tianjin Key Lab of Radiation Medicine Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. wangyan@irm-cams.ac.cn.Department of Cellular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China. yangbingtj@aol.com.Tianjin Key Lab of Radiation Medicine Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. heningning@irm-cams.ac.cn.Tianjin Key Lab of Radiation Medicine Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. wangjinhan@irm-cams.ac.cn.Tianjin Key Lab of Radiation Medicine Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. jikaihua@irm-cams.ac.cn.Tianjin Key Lab of Radiation Medicine Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. liuyang@irm-cams.ac.cn.Tianjin Key Lab of Radiation Medicine Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. liuqiang@irm-cams.ac.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30544713

Citation

Wang, Qin, et al. "Melatonin Sensitizes Human Colorectal Cancer Cells to Γ-ray Ionizing Radiation in Vitro and in Vivo." International Journal of Molecular Sciences, vol. 19, no. 12, 2018.
Wang Q, Sun Z, Du L, et al. Melatonin Sensitizes Human Colorectal Cancer Cells to γ-ray Ionizing Radiation In Vitro and In Vivo. Int J Mol Sci. 2018;19(12).
Wang, Q., Sun, Z., Du, L., Xu, C., Wang, Y., Yang, B., He, N., Wang, J., Ji, K., Liu, Y., & Liu, Q. (2018). Melatonin Sensitizes Human Colorectal Cancer Cells to γ-ray Ionizing Radiation In Vitro and In Vivo. International Journal of Molecular Sciences, 19(12). https://doi.org/10.3390/ijms19123974
Wang Q, et al. Melatonin Sensitizes Human Colorectal Cancer Cells to Γ-ray Ionizing Radiation in Vitro and in Vivo. Int J Mol Sci. 2018 Dec 10;19(12) PubMed PMID: 30544713.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Melatonin Sensitizes Human Colorectal Cancer Cells to γ-ray Ionizing Radiation In Vitro and In Vivo. AU - Wang,Qin, AU - Sun,Zhijuan, AU - Du,Liqing, AU - Xu,Chang, AU - Wang,Yan, AU - Yang,Bing, AU - He,Ningning, AU - Wang,Jinhan, AU - Ji,Kaihua, AU - Liu,Yang, AU - Liu,Qiang, Y1 - 2018/12/10/ PY - 2018/11/14/received PY - 2018/12/04/revised PY - 2018/12/07/accepted PY - 2018/12/15/entrez PY - 2018/12/14/pubmed PY - 2019/3/26/medline KW - colorectal cancer KW - ionizing radiation KW - melatonin KW - radiosensitivity JF - International journal of molecular sciences JO - Int J Mol Sci VL - 19 IS - 12 N2 - Colorectal cancer is the most commonly reported gastrointestinal malignancy, with a recent, rapid increase of the annual incidence all over the world. Enhancing the radiosensitivity of cancer cells while preserving the health of normal cells is one of the most important tasks in clinical radiobiology. However, resistance to radiotherapy for colorectal cancer greatly decreases the therapeutic outcome. Melatonin (N-acetyl-5-methoxytryptamine), a natural secretory product that the pineal gland in the brain normally produces, has been reported to have anticancer properties. In the study, we investigated the combination of melatonin with radiotherapy as a treatment for colorectal cancer. We firstly explored the anti-tumor activity of melatonin combined with ionizing radiation (IR) against colorectal carcinoma in vitro. It was found that melatonin effectively inhibited human colorectal carcinoma cell line HCT 116 cellular proliferation, colony formation rate and cell migration counts following IR. Increasing the radiosensitivity of colorectal cancer cells by melatonin treatment was found to be associated with cell cycle arrest in the G2/M phase, downregulation of proteins involved in DNA double-strand break repair and activation of the caspase-dependent apoptotic pathway. Moreover, we also investigated the combined effect of IR and melatonin on colorectal tumor in vivo. Results from a tumor xenograft showed that melatonin plus IR treatment significantly suppressed tumor cell growth compared with melatonin or IR alone, resulting in a much higher tumor inhibition rate for the combined treatment. The data suggested that melatonin combined with IR could improve the radiosensitivity of colorectal cancer and thus enhance the therapeutic effect of the patients, implying melatonin could function as a potential sensitizer in tumor radiotherapy. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/30544713/Melatonin_Sensitizes_Human_Colorectal_Cancer_Cells_to_γ_ray_Ionizing_Radiation_In_Vitro_and_In_Vivo_ DB - PRIME DP - Unbound Medicine ER -