Identification of natural compound garcinone E as a novel autophagic flux inhibitor with anticancer effect in nasopharyngeal carcinoma cells.

Abstract

CONTEXT:

Current chemotherapeutic drugs cannot meet the treatment needs of patients with nasopharyngeal carcinoma (NPC), so urgent action is needed to discover novel chemotherapeutic agents. Our previous study revealed that garcinone E (GE) inhibited the proliferation and metastasis of NPC, suggesting that the compound might display promising anticancer activity.

OBJECTIVE:

To examine the mechanism underlying the anti-NPC activity of GE for the first time.

MATERIALS AND METHODS:

For MTS assay, NPC cells were treated with 2.5-20 μmol/L GE or dimethyl sulfoxide for 24, 48, and 72 h. Colony formation capacity, cell cycle distribution, and in vivo xenograft experiment of GE were assessed. MDC staining, StubRFP-sensGFP-LC3 observation, LysoBrite Blue staining, and immunofluorescence examined the autophagy of NPC cells after GE exposure. Western blotting, RNA-sequencing, and RT-qPCR measured protein and mRNA levels.

RESULTS:

GE suppressed cell viability with an IC50 of 7.64, 8.83 and 4.65 μmol/L for HK1, HONE1 and S18 cells. GE inhibited colony formation and cell cycle, increased autophagosome number, and inhibited the autophagic flux partially by blocking lysosome-autophagosome fusion, and repressed S18 xenograft growth. GE dysregulated the expression of autophagy- and cell cycle-related proteins such as Beclin-1, SQSTM1/p62, LC3, CDKs, and Cyclins. Bioinformatics GO and KEGG pathway enrichment analysis of RNA-seq showed that autophagy was enriched in differentially expressed genes upon GE treatment.

DISCUSSION AND CONCLUSION:

GE acts as an autophagic flux inhibitor, which may have potential chemotherapeutic use for NPC treatment and may have an application in basic research to explore the mechanisms of autophagy.

• Authors: Dan Wei, Luolin Wang, Shunmei Lei, Han Zhang, Caihua Dong, Yao Ke, Yuting Su, Xiaoying Chen, Lianping Xia, Xiaoyang Kong, Fuqiang Yin, Xia Liu
• Journal: Pharmaceutical biology (Pharm Biol) Vol. 61 Issue 1 Pg. 839-857 (Dec 2023) ISSN: 1744-5116 [Electronic] England
• PMID: 37203204 (Publication Type: Journal Article)

Chemical References

• garcinone E

Topics

• Humans
• Nasopharyngeal Carcinoma (drug therapy, metabolism)
• Cell Proliferation
• Apoptosis
• Autophagy
• Cell Line, Tumor
• Nasopharyngeal Neoplasms (drug therapy, metabolism, pathology)