Effects and Mechanisms of Fucoxanthin from Hizikia fusiforme on Inhibiting Tongue Squamous Cell Carcinoma Proliferation via AKT/mTOR-Mediated Glycolysis

Abstract

Fucoxanthin, a natural carotenoid, contains special ene bonds and 5, 6-mono-epoxide compounds in its molecule, which has physiological activities such as anticancer, antioxidant, anti-inflammatory, antiobesity, and antidiabetic. However, the anticancer actions and underlying mechanisms of fucoxanthin on oral cancer remain to be assessed. In this study, we used tongue carcinoma (CAL-27) cells to examine the effects and underlying mechanisms of fucoxanthin derived from Hizikia fusiforme on CAL-27 proliferation. MTT assays were used to estimate fucoxanthin’s effect on the proliferative capacity of CAL-27 cells. Flow cytometry was used to examine how fucoxanthin affects apoptosis initiation and alters cell cycle progression in CAL-27 cells. Spectrophotometry was used to assess the impact of fucoxanthin on adenosine triphosphate (ATP) generation, glucose uptake, lactate production, and the enzymatic activities of pyruvate kinase and hexokinase in CAL-27 cells. Western blotting was used to investigate fucoxanthin’s impact on the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway and glycolysis-related protein expression levels in CAL-27 cells. Fucoxanthin significantly inhibited CAL-27 cell viability time- and dose-dependently p < 0.01 . Administration of fucoxanthin induced CAL-27 cell apoptosis and cell cycle arrest at the G1 phase p < 0.05 . Furthermore, fucoxanthin significantly decreased glucose uptake, lactate production, and ATP production in CAL-27 cells p < 0.01 and significantly inhibited glycolysis-related enzyme activities and protein expression levels p < 0.05 . Fucoxanthin also substantially decreased the expression levels of phosphorylated ribosomal protein S6, phosphorylated AKT, and phosphorylated mTOR p < 0.05 . In conclusion, fucoxanthin inhibited CAL-27 cell proliferation, and this mechanism may be associated with the AKT/mTOR-mediated glycolysis pathway.

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

“…Recent investigations have further demonstrated compound 32 as a potential anticancer lead against multiple carcinomas. 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 ].…”

Fucoxanthin Induces Ferroptosis in Cancer Cells via Downregulation of the Nrf2/HO−1/GPX4 Pathway

“…The molecular mechanism may involve upregulation of cyclin−dependent kinase inhibitor protein expression and downregulation of one or more cyclin−dependent kinases [ 8 ]. Additionally, recent research indicated that fucoxanthin inhibits tongue cancer CAL−27 cell migration and invasion by inhibiting the expression of protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway components [ 9 ]. Similarly, fucoxanthin promotes apoptosis and autophagy in mouse cancer cells by reducing the phosphorylation of Akt, its downstream proteins, and apoptosis−related proteins; it also reduces DNA damage in normal cells and tumor cell metastasis and invasion by inhibiting chronic inflammation [ 10 , 11 , 12 ].…”