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
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  • Published online on: January 20, 2015     https://doi.org/10.3892/or.2015.3738
  • Pages: 1443-1449
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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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March-2015
Volume 33 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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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