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

Wei, Dan1,2; Wang, Luolin3,4; Lei, Shunmei1,2; Zhang, Han1,2; Dong, Caihua1,2,5,6,7; Ke, Yao8,9; Su, Yuting8,9; Chen, Xiaoying8,9; Xia, Lianping8,9; Kong, Xiaoyang1; Yin, Fuqiang8,9,10; Liu, Xia1,2,5,6,7,10

2023-12-31

10.1080/13880209.2023.2210187

PHARMACEUTICAL BIOLOGY   影响因子和分区

1388-0209

1744-5116

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 mu mol/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 mu mol/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.

Autophagy autophagosome cell cycle arrest RNA-seq KEGG pathway enrichment

SCI

英语

其他

National Natural Science Foundation of China["82260721","81903644","81660606","81860458"] ; Guangxi Natural Science Foundation["2018GXNSFAA281227","2021GXNSFAA075002"] ; Advanced Innovation Teams and Xinghu Scholars Program of Guangxi Medical University[24/02304001018X] ; Innovation Project of Guangxi Graduate Education[YCSW2022215]

Plant Sciences ; Medical Laboratory Technology ; Pharmacology & Pharmacy

Plant Sciences ; Medical Laboratory Technology ; Pharmacology & Pharmacy

WOS:000990875400001

TAYLOR & FRANCIS LTD

PHARMACOLOGY & TOXICOLOGY

Web of Science

1.Guangxi Med Univ, Ctr Translat Med, Key Lab Longev & Ageing Related Dis Chinese Minist, Nanning, Guangxi, Peoples R China
2.Guangxi Med Univ, Sch Preclin Med, Nanning, Guangxi, Peoples R China
3.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Gastroenterol, Shenzhen, Guangdong, Peoples R China
4.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen, Guangdong, Peoples R China
5.Guangxi Key Lab Regenerat Med, Collaborat Innovat Ctr Regenerat Med & Med BioReso, Nanning, Guangxi, Peoples R China
6.Guangxi Med Univ, Inst Neurosci, Dept Human Anat, Nanning, Guangxi, Peoples R China
7.Guangxi Med Univ, Sch Basic Med Sci, Guangxi Key Lab Brain Sci, Nanning, Guangxi, Peoples R China
8.Guangxi Med Univ, Key Lab High Incidence Tumour Prevent & Treatment, Minist Educ, Nanning, Guangxi, Peoples R China
9.Guangxi Med Univ, Life Sci Inst, Nanning, Guangxi, Peoples R China
10.Guangxi Med Univ, Nanning 530021, Guangxi, Peoples R China

Wei, Dan,Wang, Luolin,Lei, Shunmei,et al. Identification of natural compound garcinone E as a novel autophagic flux inhibitor with anticancer effect in nasopharyngeal carcinoma cells[J]. PHARMACEUTICAL BIOLOGY,2023,61(1).

Wei, Dan.,Wang, Luolin.,Lei, Shunmei.,Zhang, Han.,Dong, Caihua.,...&Liu, Xia.(2023).Identification of natural compound garcinone E as a novel autophagic flux inhibitor with anticancer effect in nasopharyngeal carcinoma cells.PHARMACEUTICAL BIOLOGY,61(1).

Wei, Dan,et al."Identification of natural compound garcinone E as a novel autophagic flux inhibitor with anticancer effect in nasopharyngeal carcinoma cells".PHARMACEUTICAL BIOLOGY 61.1(2023).