Research Papers:

Melatonin exerts anti-oral cancer effect via suppressing LSD1 in patient-derived tumor xenograft models

Cheng-Yu Yang, Chih-Kung Lin, Chang-Huei Tsao, Cheng-Chih Hsieh, Gu-Jiun Lin, Kuo-Hsing Ma, Yi-Shing Shieh, Huey-Kang Sytwu and Yuan-Wu Chen _

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Oncotarget. 2017; 8:33756-33769. https://doi.org/10.18632/oncotarget.16808

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Cheng-Yu Yang1,6, Chih-Kung Lin3, Chang-Huei Tsao7,8, Cheng-Chih Hsieh5, Gu-Jiun Lin4, Kuo-Hsing Ma4, Yi-Shing Shieh6, Huey-Kang Sytwu1,7 and Yuan-Wu Chen1,2,6

1Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan

2Department of Oral and Maxillofacial Surgery, Tri-Service General Hospital, Taipei, Taiwan

3Division of Anatomic Pathology, Taipei Tzu Chi Hospital, Taipei, Taiwan

4Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan

5Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan

6School of Dentistry, National Defense Medical Center, Taipei, Taiwan

7Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan

8Department of Medical Research, Tri-Service General Hospital, Taipei, Taiwan

Correspondence to:

Yuan-Wu Chen, email: [email protected]

Keywords: patient-derived tumor xenograft, LSD1, melatonin, oral cancer, cell proliferation

Received: June 16, 2016     Accepted: March 08, 2017     Published: April 04, 2017


Aberrant activation of histone lysine-specific demethylase (LSD1) increases tumorigenicity; hence, LSD1 is considered a therapeutic target for various human cancers. Although melatonin, an endogenously produced molecule, may defend against various cancers, the precise mechanism involved in its anti-oral cancer effect remains unclear. Patient-derived tumor xenograft (PDTX) models are preclinical models that can more accurately reflect human tumor biology compared with cell line xenograft models. Here, we evaluated the anticancer activity of melatonin by using LSD1-overexpressing oral cancer PDTX models. By assessing oral squamous cell carcinoma (OSCC) tissue arrays through immunohistochemistry, we examined whether aberrant LSD1 overexpression in OSCC is associated with poor prognosis. We also evaluated the action mechanism of melatonin against OSCC with lymphatic metastases by using the PDTX models. Our results indicated that melatonin, at pharmacological concentrations, significantly suppresses cell proliferation in a dose- and time-dependent manner. The observed suppression of proliferation was accompanied by the melatonin-mediated inhibition of LSD1 in oral cancer PDTXs and oral cancer cell lines. In conclusion, we determined that the beneficial effects of melatonin in reducing oral cancer cell proliferation are associated with reduced LSD1 expression in vivo and in vitro.

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