Melatonin reduces lung cancer stemness through inhibiting of PLC, ERK, p38, β-catenin, and Twist pathways

doi:10.1002/tox.22674

. 2019 Feb;34(2):203-209.

doi: 10.1002/tox.22674. Epub 2018 Nov 12.

Melatonin reduces lung cancer stemness through inhibiting of PLC, ERK, p38, β-catenin, and Twist pathways

Yi-Chen Yang¹, Pei-Chen Chiou², Po-Chun Chen³, Po-Yi Liu^{4

5}, Wei-Chien Huang⁴, Chia-Chia Chao⁶, Chih-Hsin Tang^{2

4

7

8}

Affiliations

¹ Department of Nursing, National Taichung University of Science and Technology, Taichung, Taiwan.
² Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
³ Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
⁴ Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan.
⁵ Department of Thoracic Surgery, Changhua Christian Hospital, Changhua, Taiwan.
⁶ Department of Respiratory Therapy, Fu-Jen Catholic University, New Taipei City, Taiwan.
⁷ Chinese Medicine Research Center, China Medical University, Taichung, Taiwan.
⁸ Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.

PMID: 30421542
DOI: 10.1002/tox.22674

Melatonin reduces lung cancer stemness through inhibiting of PLC, ERK, p38, β-catenin, and Twist pathways

Yi-Chen Yang et al. Environ Toxicol. 2019 Feb.

. 2019 Feb;34(2):203-209.

doi: 10.1002/tox.22674. Epub 2018 Nov 12.

Authors

Yi-Chen Yang¹, Pei-Chen Chiou², Po-Chun Chen³, Po-Yi Liu^{4

5}, Wei-Chien Huang⁴, Chia-Chia Chao⁶, Chih-Hsin Tang^{2

4

7

8}

Affiliations

¹ Department of Nursing, National Taichung University of Science and Technology, Taichung, Taiwan.
² Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
³ Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
⁴ Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan.
⁵ Department of Thoracic Surgery, Changhua Christian Hospital, Changhua, Taiwan.
⁶ Department of Respiratory Therapy, Fu-Jen Catholic University, New Taipei City, Taiwan.
⁷ Chinese Medicine Research Center, China Medical University, Taichung, Taiwan.
⁸ Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.

PMID: 30421542
DOI: 10.1002/tox.22674

Abstract

Lung cancer is one of the most common cancer in cancer-related deaths worldwide, which is characterized by its strong metastatic potential. The melatonin hormone secreted by the pineal grand has an antioxidant effect and protects cells against carcinogenic substances. However, the effects of melatonin in lung cancer stemness are largely unknown. We found that melatonin reduces CD133 expression by ~50% in lung cancer cell lines, while results of a sphere formation assay showed that melatonin inhibits lung cancer stemness. These effects of melatonin were reversed when the cell lines were incubated with phospholipase C (PLC), ERK/p38, and a β-catenin activator. Transfection with Twist siRNA augmented the inhibitory effects of melatonin, indicating that melatonin suppresses lung cancer stemness by inhibiting the PLC, ERK/p38, β-catenin, and Twist signaling pathways. We also found CD133 expression is positively correlated with Twist expression in lung cancer specimens. Melatonin shows promise in the treatment of lung cancer stemness and deserves further study.

Keywords: Twist; lung cancer; melatonin; stemness.

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Melatonin reduces lung cancer stemness through inhibiting of PLC, ERK, p38, β-catenin, and Twist pathways

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Melatonin reduces lung cancer stemness through inhibiting of PLC, ERK, p38, β-catenin, and Twist pathways

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