Page 233 - 2025中醫藥與天然藥物聯合學術研討會-中醫藥與天然藥物的挑戰Ｘ機遇與未來大會手冊

PP-50

Melatonin inhibits bone cancer anoikis resistance and metastasis by

suppressing SLC38A5 expression and glutamine metabolism

2
Nguyen Bao Tran, #,1 Kun-Tsan Lee, Chih-Hsin Tang* ,1,3,4

1 Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
2 Department of Post-Baccalaureate Medicine, National Chung-Hsing University, Taichung,
Taiwan
3 Department of Pharmacology, School of Medicine, China Medical University, Taichung,
Taiwan
4 Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
* E-mail: chtang@mail.cmu.edu.tw

Abstract
Malignant bone cancer, including osteosarcoma and chondrosarcoma as popular subtypes,
are aggressive neoplasms which arise from bone tissue and have lung metastasis. Anoikis
resistance is one of the crucial steps of cancer metastasis. Melatonin is a hormone produced by
the pineal gland and exhibits anticarcinogenic properties in the development and progression
of certain types of bone cancer. Little is known about clearing bone cancer cell anoikis
resistance and how melatonin could therapeutically unactivated this process. We demonstrated
that glutamine metabolism is essential for bone cancer cells to resist anoikis. Melatonin
regulates glutamine metabolism to reduce bone cancer cell anoikis resistance and metastasis.
Interestingly, higher amino acid solute carrier family 38 member 5 (SLC38A5), a glutamine
transporter in bone tumor is positively associated with cancer progression. Melatonin inhibited
SLC38A5 expression and restricted bone cancer cell anoikis resistance via the PI3K/Akt
pathway. Accordingly, we found that the reduction of SLC38A5 levels is associated with
decreased metastasis in melatonin-treated groups in the orthotopic mouse model. Overall, our
study contributes to clarifying the anticancer mechanism of melatonin in bone cancer anoikis
resistance and metastasis. In addition, this study supports SLC38A5 and glutamine metabolism
as potential candidates for bone cancer treatment investigation.

Keywords: Bone cancer; Glutamine metabolism; Anoikis resistance; SLC38A5; Metastasis