Curcumin analog, GO-Y078, induces HO-1 transactivation-mediated apoptotic cell death of oral cancer cells by triggering MAPK pathways and AP-1 DNA-binding activity. (3rd April 2022)

• Record Type: Journal Article
• Authors: Chien, Ming-Hsien; Shih, Pei-Chun; Ding, Yi-Fang; Chen, Li-Hsin; Hsieh, Feng-Koo; Tsai, Meng-Ying; Li, Pei-Yi; Lin, Chiao-Wen; Yang, Shun-Fa
• Is Part Of: Expert opinion on therapeutic targets. Volume 26:Number 4(2022)
• Page Start: 375
• Page End: 388
• Publication Date: 2022-04-03
• Subjects: Oral squamous cell carcinoma -- GO-Y078 -- heme oxygenase-1 -- activator protein 1; Drugs -- Research -- Periodicals; 615.072
• DOI: 10.1080/14728222.2022.2061349
• Languages: English
• ISSNs: 1744-7631

Abstract

ABSTRACT: Background: GO-Y078, a new synthetic analogue of curcumin (CUR), has higher oral bioavailability and anticancer activity than CUR, but the oncostatic effect of GO-Y078 on oral squamous cell carcinoma (OSCC) is largely unknown. Research design and methods: In the present study, we examined the oncostatic properties and possible mechanisms of GO-Y078 on human SCC-9 and HSC-3 OSCC cells. Results: Our results indicated that GO-Y078 showed a cytostatic effect against OSCC cells, and this antiproliferative phenomenon stemmed from a mechanism involving multiple levels of cooperation, including cell-cycle G2 /M arrest and apoptosis induction. Mechanistically, GO-Y078 treatment induced caspase-mediated apoptosis via upregulating two apoptosis-modulating proteins, SMAC/DIABLO and heme oxygenase (HO)-1. GO-Y078 transcriptionally induced upregulation of the HO-1 gene by increasing the AP-1 DNA-binding activity, which was initiated by activation of the p38 /JNK1/2 pathways. In the clinic, patients with head and neck cancers expressed lower HO-1 and SMAC/DIABLO levels in primary cancer tissues compared to normal tissues. Clinical datasets also revealed that patients with head and neck cancers expressing high HO-1 had afavorable prognosis. Conclusions: Our results provide new insights into the role of GO-Y078-induced molecular regulation in suppressing OSCC growth and suggest that GO-Y078 has potential therapeutic applications for OSCC.