fucoxanthin and Breast-Neoplasms

Breast cancer (BC) is one of the most common cancers diagnosed and the leading cause of cancer-related death in women. Although there are first-line treatments for BC, drug resistances and adverse events have been reported. Given the incidence of BC keeps increasing, seeking novel therapeutics is urgently needed. Fucoxanthin (Fx) is a dietary carotenoid commonly found in seaweeds and diatoms. Both in vitro and in vivo studies show that Fx and its deacetylated metabolite fucoxanthinol (Fxol) inhibit and prevent BC growth. The NF-κB signaling pathway is considered the major pathway contributing to the anti-proliferation, anti-angiogenesis and pro-apoptotic effects of Fx and Fxol. Other signaling molecules such as MAPK, MMP2/9, CYP and ROS are also involved in the anti-cancer effects by regulating the tumor microenvironment, cancer metastasis, carcinogen metabolism and oxidation. Besides, Fx also possesses anti-obesity effects by regulating UCP1 levels and lipid metabolism, which may help to reduce BC risk. More importantly, mounting evidence demonstrates that Fx overcomes drug resistance. This review aims to give an updated summary of the anti-cancer effects of Fx and summarize the underlying mechanisms of action, which will provide novel strategies for the development of Fx as an anti-cancer therapeutic agent.

Topics: Breast Neoplasms; Female; Humans; NF-kappa B; Signal Transduction; Tumor Microenvironment; Xanthophylls

Fucoxanthin (Fx) is a carotenoid derived from marine organisms that exhibits anticancer activities. However, its role as a potential drug adjuvant in breast cancer (BC) treatment is still poorly explored. Firstly, this study investigated the cytotoxic effects of Fx alone and combined with doxorubicin (Dox) and cisplatin (Cis) on a panel of 2D-cultured BC cell lines (MCF7, SKBR3 and MDA-MB-231) and one non-tumoral cell line (MCF12A). Fucoxanthin induced cytotoxicity against all the cell lines and potentiated Dox cytotoxic effects towards the SKBR3 and MDA-MB-231 cells. The combination triggering the highest cytotoxicity (Fx 10 µM + Dox 1 µM in MDA-MB-231) additionally showed significant induction of cell death and genotoxic effects, relative to control. In sequence, the same combination was tested on 3D cultures using a multi-endpoint approach involving bioactivity assays and microscopy techniques. Similar to 2D cultures, the combination of Fx and Dox showed higher cytotoxic effects on 3D cultures compared to the isolated compounds. Furthermore, this combination increased the number of apoptotic cells, decreased cell proliferation, and caused structural and ultrastructural damages on the 3D models. Overall, our findings suggest Fx has potential to become an adjuvant for Dox chemotherapy regimens in BC treatment.

Topics: Adjuvants, Pharmaceutic; Antineoplastic Agents; Breast Neoplasms; Cell Culture Techniques; Cell Death; Cell Line, Tumor; Cell Proliferation; Cisplatin; Doxorubicin; Drug Synergism; Female; Humans; Xanthophylls

Tumour lymphangiogenesis plays an important role in promoting the growth and lymphatic metastasis of tumours. The process is associated with cell proliferation, migration and tube-like structure formation in lymphatic endothelial cells (LEC), but no antilymphangiogenic agent is currently used in clinical practice. Fucoxanthin is a material found in brown algae that holds promise in the context of drug development. Fucoxanthin is a carotenoid with variety of pharmacological functions, including antitumour and anti-inflammatory effects. The ability of fucoxanthin to inhibit lymphangiogenesis remains unclear. The results of experiments performed as part of this study show that fucoxanthin, extracted from Undaria pinnatifida (Wakame), inhibits proliferation, migration and formation of tube-like structures in human LEC (HLEC). In this study, fucoxanthin also suppressed the malignant phenotype in human breast cancer MDA-MB-231 cells and decreased tumour-induced lymphangiogenesis when used in combination with a conditional medium culture system. Fucoxanthin significantly decreased levels of vascular endothelial growth factor (VEGF)-C, VEGF receptor-3, nuclear factor kappa B, phospho-Akt and phospho-PI3K in HLEC. Fucoxanthin also decreased micro-lymphatic vascular density (micro-LVD) in a MDA-MB-231 nude mouse model of breast cancer. These findings suggest that fucoxanthin inhibits tumour-induced lymphangiogenesis in vitro and in vivo, highlighting its potential use as an antilymphangiogenic agent for antitumour metastatic comprehensive therapy in patients with breast cancer.

Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Endothelial Cells; Female; Humans; Lymphangiogenesis; Lymphatic Vessels; Mice, Inbred BALB C; Mice, Nude; Phaeophyceae; Vascular Endothelial Growth Factor C; Vascular Endothelial Growth Factor Receptor-3; Xanthophylls; Xenograft Model Antitumor Assays

We evaluated whether low doses of the natural carotenoid fucoxanthin and/or of its metabolite fucoxanthinol are effective against proliferation of estrogen-sensitive MCF-7 and estrogen-resistant MDA-MB-231 breast cancer cell lines.. These cell lines were stimulated with 10 to 20 μM fucoxanthin and/or fucoxanthinol, followed by cell viability assays, Annexin V immunofluorescence to evaluate apoptosis, as well as mRNA and protein extractions for changes in nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) members' expressions and nuclear translocations.. Fucoxanthin and fucoxanthinol reduced the viability of MCF-7 and MDA-MB-231 cells in a time-dependent manner as a result of increased apoptosis. In both cell lines, modulatory actions of fucoxanthinol on members of the NF-κB pathway were more pronounced than that of fucoxanthin.. In MDA-MB-231 cells, fucoxanthinol reduced nuclear levels of NF-κB members' p65, p52 and RelB. Fucoxanthinol and fucoxanthin could be effective for the treatment and/or prevention of breast cancer.

Topics: Antineoplastic Agents; Apoptosis; Apoptosis Regulatory Proteins; beta Carotene; Breast Neoplasms; Cell Nucleus; Cell Proliferation; Cell Survival; Drug Screening Assays, Antitumor; Female; Gene Expression; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; NF-kappa B; SOX9 Transcription Factor; Xanthophylls

Fucoxanthin is a carotenoid present in the chloroplasts of brown seaweeds. When ingested, it is metabolized mainly to fucoxanthinol in the gastrointestinal tract by digestive enzymes. These compounds have been shown to have many beneficial health effects. The present study was designed to evaluate the molecular mechanisms of action of fucoxanthin and/or of its metabolite fucoxanthinol against viability of estrogen-sensitive MCF-7 and estrogen-resistant MDA-MB-231 breast cancer cell lines. Fucoxanthin and fucoxanthinol reduced the viability of MCF-7 and MDA-MB-231 cells in dose- and time-dependent manners as a result of increased apoptosis. Furthermore, fucoxanthinol-induced apoptosis was more potent than that of fucoxanthin and correlated, for MDA-MB-231 cells, with inhibitory actions on members of the NF-κB pathway p65, p50, RelB, and p52. Being overexpressed and regulated by NF-κB in different types of cancers, the transcription factor SOX9 was also decreased at the nuclear level by fucoxanthin and fucoxanthinol in MDA-MB-231. Taken together, the current results suggest that fucoxanthinol and fucoxanthin could be potentially effective for the treatment and/or prevention of different types of cancers, including breast cancer.

Topics: Apoptosis; beta Carotene; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; Female; Humans; MCF-7 Cells; NF-kappa B p50 Subunit; NF-kappa B p52 Subunit; Poly(ADP-ribose) Polymerases; Signal Transduction; SOX9 Transcription Factor; Transcription Factor RelA; Transcription Factor RelB; Xanthophylls