Synergistic suppressive effects on triple-negative breast cancer by the combination of JTC-801 and sodium oxamate

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Title:	Synergistic suppressive effects on triple-negative breast cancer by the combination of JTC-801 and sodium oxamate
Authors:	王智揚 Wang, Chih-Yang;Xuan, Do Thi Minh;Ye, Pei-Hsuan;Li, Chung-Yen;Anuraga, Gangga;Ta, Hoang Dang Khoa;Lai, Ming-Derg;Hsu, Hui-Ping
Contributors:	癌症生物學與藥物研發博士學位學程
Keywords:	JTC-801;Triple-negative breast cancer;cell metabolism;glycolysis;sodium oxamate;synergistic effect
Date:	2023-10
Issue Date:	2024-12-04 14:05:56 (UTC+8)
Abstract:	Triple-negative breast cancer (TNBC) poses a significant clinical challenge due to the limited targeted therapies available at present. Cancer cells preferentially use glycolysis as their primary source of energy; characterized by increased glucose uptake and lactate production. JTC-801; a nociception/orphanin FQ opioid peptide (NOP) receptor antagonist; was reported to suppress the opioid receptor-like1 (ORL1) receptor/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor (NF)-κB-mediated carbonic anhydrase 9 (CA9) signaling pathway. Sodium oxamate is an inhibitor of gluconeogenesis and a glycolysis inhibitor; as a competitive lactate dehydrogenase A (LDHA) inhibitor; which also produces tumor suppression due to loss of LDHA activity. However; the roles of opioid analgesic drugs (e.g.; JTC-801) and glycolysis inhibitors (e.g.; sodium oxamate) in TNBC have not fully been explored. Meanwhile; concurrent treatment with JTC-801 and sodium oxamate may cause synergistic anticancer effects in a TNBC model. In the present study; the combination of JTC-801 and sodium oxamate triggered cell death in the TNBC MDA MB-231 cell line. RNA-sequencing data revealed potential genes in the crosstalk between JTC-801 and sodium oxamate including ALDOC; DDIT4; DHTKD1; EIF6; ENO1; ENO3; FOXK1; FOXK2; HIF1A; MYC; PFKM; PFKP; PPARA; etc. The combination of JTC-801 and sodium oxamate provides a novel potential therapeutic strategy for TNBC patients via downregulating cell cycle- and amino acid metabolism-related pathways such as "Cell cycle-the metaphase checkpoint" "(L)-tryptophan pathways and transport" and "Glutamic acid pathway". Collectively; the present study demonstrated that the synergistic effect of co-treatment with JTC-801 and sodium oxamate significantly suppressed tumor growth and played a crucial role in tumor development; and in turn may serve as potential synergistic drugs for TNBC.
Relation:	American journal of cancer research; 13(10); 4661–4677
Description:	【112-2 升等】臺北醫學大學教師升等專門著作職別：專任送審等級：副教授著作送審
Note:	代表著作名稱：《Synergistic suppressive effects on triple-negative breast cancer by the combination of JTC-801 and sodium oxamate》 AJCR Copyright ? 2023.
Data Type:	article
Appears in Collections:	[Scholarly output for promotion] 112 [ PhD Program in Cancer Biology and Drug Research] Periodical Articles

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