Fucoxanthin may inhibit cervical cancer cell proliferation via downregulation of HIST1H3D

Abstract

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.

A Systematic Review on Marine Algae-Derived Fucoxanthin: An Update of Pharmacological Insights

“…Fucoxanthin also effectively suppressed the cell proliferation and colony formation in cervical cancer cells in molecular mechanisms of inducing apoptosis and decreasing the expression of histone cluster 1 H3 family member D (HIST1H3D) [ 56 ]. Murase et al [ 57 ] reported the anti-tumor effects of fucoxanthin in c57bl/6j mice with decreased expressions of the chemokine (C-C motif) ligand 21 (CCL21)/chemokine receptor 7 (CCR7) axis.…”

Fucoxanthin Inhibits the Proliferation of ABCC2-Over Expressing Cisplatin-Resistance Ovarian Cancer Cells via Inducing Apoptosis

“…There are many pharmacological evidence about its health-promoting effects including anti-cancer 13 and anti-inflammatory properties, 14 its protective effects against doxorubicin-induced cardiotoxicity, 15 Pharmaceutical Sciences (Indexed in ISI and Scopus) https://ps.tbzmed.ac.ir/ diabetic nephropathy, 16 alcoholic liver injury 17 and other metabolic disease. The multi-potent health effects of fucoxanthin are attributed to its unique chemical structure including an allenic bond, an acetyl group, a conjugated carbonyl group, and 5,6-monoepoxide.…”

Marine-Derived Anticancer Agents Targeting Apoptotic Pathways: Exploring the Depths for Novel Cancer Therapies

“…Compound 32 facilitated apoptosis and downregulated MMP gene expression in tongue cancer cell lines (CAL-27) [ 194 ]. Additionally, it demonstrated antiproliferative properties against CAL-27 cell lines through alteration of glucose uptake and inactivation of protein kinase B/mammalian target of the rapamycin (Akt/mTOR) signaling pathway [ 195 ]. Moreover, compound 32 could promote cervical cancer cell (HeLa and SiHa) proliferation by suppressing histone Cluster 1 H3 Family Member D (HIST1H3D) expression and arresting the G0/G1 cell cycle [ 195 ].…”