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Fucoxanthin may inhibit cervical cancer cell proliferation via downregulation of HIST1H3D
Guoliu Ye1, Lingling Wang1, Kang Yang1
1Department of Obstetrics and Gynaecology, the First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
Objective:
To investigate the role of fucoxanthin, reported to have significant anticancer effects, and histone Cluster 1 H3 Family Member D (HIST1H3D; implicated in tumorigenesis) in cervical cancer.
Methods:
The half maximal inhibitory concentration (IC50) of fucoxanthin against HeLa and SiHa cervical cancer cells was determined. Differentially expressed genes (DEGs) in SiHa cells treated with IC50 fucoxanthin were screened by high-throughput techniques and subjected to signal enrichment. Following identification of HIST1H3D as a candidate gene, HIST1H3D-knockdown models were created via transfection with a short hairpin HIST1H3D payload. Impacts on cell proliferation, cell-cycle distribution, colony formation, and apoptosis were studied.
Results:
The fucoxanthin IC50 was 1 445 and 1 641 µM (Hela and SiHa cells, respectively). Chip results revealed 2 255 DEGs, including 943 upregulated and 1 312 downregulated genes, in fucoxanthin-treated versus untreated SiHa cells. Disease and function analysis indicated that these DEGs are primarily associated with cancer and organismal injuries and abnormalities, and online integrated pathway analysis showed that the DEGs were mainly enriched in p53 signalling. HIST1H3D was significantly downregulated in response to fucoxanthin. Inhibition of HIST1H3D mRNA significantly reduced cell proliferation and colony formation, significantly augmented the percentage of apoptotic HeLa and SiHa cells, and cells were arrested in G0/G1 cell cycle phase.
Conclusion:
The results suggest that HIST1H3D may be an oncogene in cervical carcinogenesis and a potential fucoxanthin target in treating cervical cancer.
Insights
Fucoxanthin shows anticancer effects by downregulating HIST1H3D, an oncogene in cervical cancer. Inhibiting HIST1H3D reduces cancer cell proliferation and promotes apoptosis, suggesting its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Cervical cancer remains a significant global health challenge.
- Fucoxanthin, a marine carotenoid, exhibits promising anticancer properties.
- Histone Cluster 1 H3 Family Member D (HIST1H3D) is implicated in tumorigenesis.
Purpose of the Study:
- To investigate the therapeutic potential of fucoxanthin in cervical cancer.
- To elucidate the role of HIST1H3D in cervical cancer progression.
- To determine if HIST1H3D is a target of fucoxanthin's anticancer effects.
Main Methods:
- Determined the half maximal inhibitory concentration (IC50) of fucoxanthin against HeLa and SiHa cervical cancer cells.
- Screened differentially expressed genes (DEGs) in fucoxanthin-treated SiHa cells using high-throughput techniques.
- Created HIST1H3D-knockdown models and assessed impacts on cell proliferation, cell cycle, colony formation, and apoptosis.
Main Results:
- Fucoxanthin treatment led to significant downregulation of HIST1H3D in SiHa cells.
- HIST1H3D inhibition significantly reduced cervical cancer cell proliferation and colony formation.
- Knockdown of HIST1H3D increased apoptosis and induced G0/G1 cell cycle arrest.
Conclusions:
- HIST1H3D acts as an oncogene in cervical carcinogenesis.
- Fucoxanthin demonstrates potential as a therapeutic agent for cervical cancer by targeting HIST1H3D.
- Targeting HIST1H3D represents a promising strategy for cervical cancer treatment.
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