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Article

Melatonin induces apoptosis in cholangiocarcinoma cell lines by activating the reactive oxygen species-mediated mitochondrial pathway

  • Authors:
    • Umawadee Laothong
    • Yusuke Hiraku
    • Shinji Oikawa
    • Kitti Intuyod
    • Mariko Murata
    • Somchai Pinlaor
  • View Affiliations / Copyright

    Affiliations: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand, Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514‑8507, Japan, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
  • Pages: 1443-1449
    |
    Published online on: January 20, 2015
       https://doi.org/10.3892/or.2015.3738
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Abstract

We previously demonstrated that melatonin could be used as a chemopreventive agent for inhibiting cholangiocarcinoma (CCA) development in a hamster model. However, the cytotoxic activity of melatonin in cancer remains unclear. In the present study, we investigated the effect of melatonin on CCA cell lines. Human CCA cell lines (KKU-M055 and KKU-M214) were treated with melatonin at concentrations of 0.5, 1 and 2 mM for 48 h. Melatonin treatment exerted a cytotoxic effect on CCA cells by inhibiting CCA cell viability in a concentration-dependent manner. Treatment with melatonin, especially at 2 mM, increased intracellular reactive oxygen species (ROS) production and in turn led to increased oxidative DNA damage and 8-oxodG formation. Moreover, melatonin treatment enhanced the production of cytochrome c leading to apoptosis in a concentration-dependent manner, as indicated by increased expression of apoptosis-related proteins caspase-3 and caspase-7. In conclusion, melatonin acts as a pro-oxidant by activating ROS-dependent DNA damage and thus leading to the apoptosis of CCA cells.
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Copy and paste a formatted citation
Spandidos Publications style
Laothong U, Hiraku Y, Oikawa S, Intuyod K, Murata M and Pinlaor S: Melatonin induces apoptosis in cholangiocarcinoma cell lines by activating the reactive oxygen species-mediated mitochondrial pathway. Oncol Rep 33: 1443-1449, 2015.
APA
Laothong, U., Hiraku, Y., Oikawa, S., Intuyod, K., Murata, M., & Pinlaor, S. (2015). Melatonin induces apoptosis in cholangiocarcinoma cell lines by activating the reactive oxygen species-mediated mitochondrial pathway. Oncology Reports, 33, 1443-1449. https://doi.org/10.3892/or.2015.3738
MLA
Laothong, U., Hiraku, Y., Oikawa, S., Intuyod, K., Murata, M., Pinlaor, S."Melatonin induces apoptosis in cholangiocarcinoma cell lines by activating the reactive oxygen species-mediated mitochondrial pathway". Oncology Reports 33.3 (2015): 1443-1449.
Chicago
Laothong, U., Hiraku, Y., Oikawa, S., Intuyod, K., Murata, M., Pinlaor, S."Melatonin induces apoptosis in cholangiocarcinoma cell lines by activating the reactive oxygen species-mediated mitochondrial pathway". Oncology Reports 33, no. 3 (2015): 1443-1449. https://doi.org/10.3892/or.2015.3738
Copy and paste a formatted citation
x
Spandidos Publications style
Laothong U, Hiraku Y, Oikawa S, Intuyod K, Murata M and Pinlaor S: Melatonin induces apoptosis in cholangiocarcinoma cell lines by activating the reactive oxygen species-mediated mitochondrial pathway. Oncol Rep 33: 1443-1449, 2015.
APA
Laothong, U., Hiraku, Y., Oikawa, S., Intuyod, K., Murata, M., & Pinlaor, S. (2015). Melatonin induces apoptosis in cholangiocarcinoma cell lines by activating the reactive oxygen species-mediated mitochondrial pathway. Oncology Reports, 33, 1443-1449. https://doi.org/10.3892/or.2015.3738
MLA
Laothong, U., Hiraku, Y., Oikawa, S., Intuyod, K., Murata, M., Pinlaor, S."Melatonin induces apoptosis in cholangiocarcinoma cell lines by activating the reactive oxygen species-mediated mitochondrial pathway". Oncology Reports 33.3 (2015): 1443-1449.
Chicago
Laothong, U., Hiraku, Y., Oikawa, S., Intuyod, K., Murata, M., Pinlaor, S."Melatonin induces apoptosis in cholangiocarcinoma cell lines by activating the reactive oxygen species-mediated mitochondrial pathway". Oncology Reports 33, no. 3 (2015): 1443-1449. https://doi.org/10.3892/or.2015.3738
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