Fucosterol Suppresses the Progression of Human Ovarian Cancer by Inducing Mitochondrial Dysfunction and Endoplasmic Reticulum Stress

Abstract

Ovarian cancer is difficult to diagnose early and has high rates of relapse and mortality. Therefore, the treatment of ovarian cancer needs to be improved. Recently, several studies have been conducted in an attempt to develop anticancer drugs from naturally derived ingredients. Compared to traditional chemotherapy, natural compounds can overcome drug resistance with lower side effects. Fucosterol, a phytosterol present in brown algae, reportedly possesses many bioactive effects, including anticancer properties. However, the anticancer effects of fucosterol in ovarian cancer remain unexplored. Therefore, we investigated the effects of fucosterol on progression in human ovarian cancer cells. Fucosterol inhibited cell proliferation and cell-cycle progression in ovarian cancer cells. Additionally, fucosterol regulated the proliferation-related signaling pathways, the production of reactive oxygen species, mitochondrial function, endoplasmic reticulum stress, angiogenesis, and calcium homeostasis. Moreover, it decreased tumor formation in a zebrafish xenograft model. These results indicate that fucosterol could be used as a potential therapeutic agent in ovarian cancer.

Cytotoxicity of Seaweed Compounds, Alone or Combined to Reference Drugs, against Breast Cell Lines Cultured in 2D and 3D

“…The combination of Fct with Cis did not differ from the effects of Cis alone. Contrary to our results, one study showed a synergistic anticancer effect of Fct in combination with Cis, related to the expression of apoptotic and angiogenic genes, in ovarian cancer cell lines [ 141 ].…”

“…This triad Fct/Dox/TNBC deserves further studies to explore the mechanisms involved in these interactions, namely using a pathway-focused gene expression analysis and additional cell-based assays. As to the latter, and because Fct may change the levels of reactive oxygen species (ROS) [ 87 , 141 ], the fine balance of which is critical for cancer cells to thrive, the determination of ROS would be a particularly relevant target in the future mechanistic assays.…”

Cytotoxic and Anti-Proliferative Effects of Fucosterol, Alone and in Combination with Doxorubicin, in 2D and 3D Cultures of Triple-Negative Breast Cancer Cells

“…At the tested conditions, Fct alone did not have cytotoxic or anti-proliferative effects on the MDA-MB-231 cells; similarly to previous studies using colon cell lines [6]. However, other study [20] reported the opposite, revealing Fct cytotoxic effects, but this was using concentrations four to twenty -times higher than those used in this study. Here, the fact that Fct in low concentration seemed to have potentiated the Dox action is a very interesting result that needs to be further explored.…”

“…Of particular importance, would be to study the mechanisms related to the interplay between Fct and Dox, namely using a pathway-focused gene expression analysis and additional cell-based assays. As to the latter, and because Fct may change the levels of reactive oxygen species (ROS) [20,21], the fine balance of which is critical for cancer cells to thrive, the determination of ROS would be a particularly interesting target.…”

Fucosterol of Marine Macroalgae: Bioactivity, Safety and Toxicity on Organism

“…Certain studies about the anticancer properties of fuscosterol extracted from marine macroalgae, such as Sargassum carpophyllum, Turbinaria conoides, Dictyota ciliolata, and Padina sanctae-crucis, have been published [21,[35][36][37][38][39]. Based on the study by Jiang et al [39], commercial fucosterols exhibit anticancer activity by inhibiting the PI3K/Akt/mTOR signaling pathway in cervical cancer cell lines.…”