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

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.

KEYWORDS:

• Oral squamous cell carcinoma
• GO-Y078
• heme oxygenase-1
• activator protein 1

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Supplementary material

Supplemental data for this article can be accessed here

Additional information

Funding

This research was supported by Chung Shan Medical University Hospital, Taiwan (CSH-2021-E-002-Y3). This study was also supported by the TMU Research Center of Cancer Translational Medicine from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan.