Cytotoxic and anti-proliferative effects of fucosterol, alone and combined with doxorubicin, in a triple-negative breast cancer cell line culture in monolayer and in a 3D system.

Fernanda Malhão; Alice Ramos; Eduardo Rocha

doi:10.3390/CAHD2020-08600

Previous Article in event

Antioxidant activity of film forming systems based on melanins from 5,6-dihydroxyindole derivatives

Previous Article in session

Total Phenolics, Total Flavonoids Contents and In Vitro Antioxidant Activity of Methanol Extract and Solvent Fractions of Desmodium ramosissimum G. Don

Next Article in event

Natural aspirin-like compounds from white willow (Salix alba) bark extract prevent structural changes of human hemoglobin during in vitro non-enzymatic glycation and fructation, preserving its peroxidase and esterase activity

Cytotoxic and anti-proliferative effects of fucosterol, alone and combined with doxorubicin, in a triple-negative breast cancer cell line culture in monolayer and in a 3D system.

Fernanda Malhão

^{*

1, 2},

Alice Abreu Ramos

^{1, 3},

Eduardo Rocha

^{*

1, 2}

¹ ICBAS - Institute of Biomedical Sciences Abel Salazar, Laboratory of Histology and Embryology, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
² CIIMAR - Interdisciplinary Center for Marine and Environmental Research, University of Porto, Avenida General Norton de Matos s/n, 4450-208 Matosinhos, Portugal.
³ CIIMAR - Interdisciplinary Center for Marine and Environmental Research, University of Porto, Avenida General Norton de Matos s/n, 4450-208 Matosinhos, Portugal

Published: 30 November 2020 by MDPI in The 1st International E-Conference on Antioxidants in Health and Disease session The Biology of Natural Products in Disease Pathophysiology: Mechanisms of Action

https://doi.org/10.3390/CAHD2020-08600

Abstract:

The triple-negative breast cancer (TNBC) has the poorest BC prognosis, as patients cannot benefit from target therapies, being chemotherapy the mainstream treatment. Therefore, the search for new drugs/drug adjuvants to overcome drug resistance or reduce their toxicity is essential. Some studies have revealed a potential synergistic effect of natural compounds (NC) in combinatorial therapy with drugs, such as doxorubicin (Dox), which is frequently used for TNBC. Fucosterol (Fct), a phytosterol from brown seaweeds, seems a promising NC, because of its antioxidant ^[1,2] and antitumor effects ^[3,4]. The mechanisms underlying these effects are still controversial. Using a TNBC cell line (MDA-MB-231), we aimed to test the effects of Fct alone and in combination with Dox on cell viability and proliferation (using MTT/resazurin and BrdU assays, respectively), in monolayer and three-dimensional (3D) cultures. Additionally, we performed a histomorphological analysis of the 3D cultures. Data demonstrated that Fct (5 µM) alone did not affect cell viability and proliferation. In monolayer, Dox (1 µM) decreased less than 50% cell viability and proliferation, while in 3D this effect was only observed in cell viability using Dox 5 µM. The combination of Fct/Dox (5/0.1 µM) in monolayer, significantly decreased cell viability and proliferation, differing from the control group and from both compounds alone. These enhanching effects of Fct in monolayer were not observed in 3D, even using higher Dox concentrations. Morphometrical analyses revealed differences in 3D areas at Dox 5 µM. We conclude that Fct may increase Dox effects under certain conditions. One possible explanatory mechanism is that Fct may activate reactive oxygen species and trigger apoptosis via mitochondrial pathways ^[5]. We further conclude that the 3D cultures of TNBC were more resistant to treatments, corroborating other studies and reinforcing the use of these more complex models for drug screening.

Acknowledgements: To UIDB/04423/2020 and UIDP/04423/2020, provided by FCT and ERDF.

[1] DOI: 10.1007/BF02976680

[2] DOI: 10.1111/jphp.12404

[3] DOI 10.3233/BME-130876

[4] DOI: 10.4103/0973-1296.93327

[5] DOI:10.18632/oncotarget.13723

Keywords: Breast cancer; Triple negative breast cancer; Fucosterol; anti-cancer activity

View paper View Poster