Environmental Toxicology

Volume 34, Issue 2 p. 203-209

RESEARCH ARTICLE

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

Yi-Chen Yang,

Yi-Chen Yang

Department of Nursing, National Taichung University of Science and Technology, Taichung, Taiwan

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Pei-Chen Chiou,

Pei-Chen Chiou

Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan

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Po-Chun Chen,

Po-Chun Chen

Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

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Po-Yi Liu,

Po-Yi Liu

Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan

Department of Thoracic Surgery, Changhua Christian Hospital, Changhua, Taiwan

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Wei-Chien Huang,

Wei-Chien Huang

Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan

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Chia-Chia Chao,

Corresponding Author

Chia-Chia Chao

[email protected]

Department of Respiratory Therapy, Fu-Jen Catholic University, New Taipei City, Taiwan

Correspondence

Chih-Hsin Tang, Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.

Email: [email protected]

Chia-Chia Chao, Department of Respiratory Therapy, Fu-Jen Catholic University, New Taipei City, Taiwan.

Email: [email protected]

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Chih-Hsin Tang,

Corresponding Author

Chih-Hsin Tang

[email protected]

orcid.org/0000-0002-7113-8352

Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan

Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan

Chinese Medicine Research Center, China Medical University, Taichung, Taiwan

Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan

Correspondence

Chih-Hsin Tang, Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.

Email: [email protected]

Chia-Chia Chao, Department of Respiratory Therapy, Fu-Jen Catholic University, New Taipei City, Taiwan.

Email: [email protected]

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Yi-Chen Yang,

Yi-Chen Yang

Department of Nursing, National Taichung University of Science and Technology, Taichung, Taiwan

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Pei-Chen Chiou,

Pei-Chen Chiou

Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan

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Po-Chun Chen,

Po-Chun Chen

Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

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Po-Yi Liu,

Po-Yi Liu

Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan

Department of Thoracic Surgery, Changhua Christian Hospital, Changhua, Taiwan

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Wei-Chien Huang,

Wei-Chien Huang

Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan

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Chia-Chia Chao,

Corresponding Author

Chia-Chia Chao

[email protected]

Department of Respiratory Therapy, Fu-Jen Catholic University, New Taipei City, Taiwan

Correspondence

Chih-Hsin Tang, Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.

Email: [email protected]

Chia-Chia Chao, Department of Respiratory Therapy, Fu-Jen Catholic University, New Taipei City, Taiwan.

Email: [email protected]

Search for more papers by this author

Chih-Hsin Tang,

Corresponding Author

Chih-Hsin Tang

[email protected]

orcid.org/0000-0002-7113-8352

Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan

Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan

Chinese Medicine Research Center, China Medical University, Taichung, Taiwan

Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan

Correspondence

Chih-Hsin Tang, Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.

Email: [email protected]

Chia-Chia Chao, Department of Respiratory Therapy, Fu-Jen Catholic University, New Taipei City, Taiwan.

Email: [email protected]

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First published: 12 November 2018

https://doi.org/10.1002/tox.22674

Citations: 53

Funding information Changhua Christian Hospital, Grant/Award Number: 106-CCH-IRP-208; Taichung Veterans General Hospital National and Taichung University of Science and Technology, Grant/Award Number: TCVGHNTUST1068502; Ministry of Education, Grant/Award Number: CMRC-CHM-3-1; National Science Council of Taiwan, Grant/Award Numbers: 107-2320-B-039-019-MY3, 107-2320-B-030-007, 106-2320-B-030-005, 106-2320-B-039-005, MOST104-2320-B-030-001

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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.

CONFLICT OF INTEREST

All authors declare that they have no financial or personal relationships with other people or organizations that could inappropriately influence this work.

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Volume34, Issue2

February 2019

Pages 203-209

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

Abstract

CONFLICT OF INTEREST

REFERENCES

Citing Literature

References

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