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.
Seaweed bioactive compounds have shown anticancer activities in in vitro and in vivo studies. However, tests remain limited, with conflicting results, and effects in combination with anticancer drugs are even scarcer. Here, the cytotoxic effects of five seaweed compounds (astaxanthin, fucoidan, fucosterol, laminarin, and phloroglucinol) were tested alone and in combination with anticancer drugs (cisplatin—Cis; and doxorubicin—Dox), in breast cell lines (three breast cancer (BC) subtypes and one non-tumoral). The combinations revealed situations where seaweed compounds presented potentiation or inhibition of the drugs’ cytotoxicity, without a specific pattern, varying according to the cell line, concentration used for the combination, and drug. Fucosterol was the most promising compound, since: (i) it alone had the highest cytotoxicity at low concentrations against the BC lines without affecting the non-tumoral line; and (ii) in combination (at non-cytotoxic concentration), it potentiated Dox cytotoxicity in the triple-negative BC cell line. Using a comparative approach, monolayer versus 3D cultures, further investigation assessed effects on cell viability and proliferation, morphology, and immunocytochemistry targets. The cytotoxic and antiproliferative effects in monolayer were not observed in 3D, corroborating that cells in 3D culture are more resistant to treatments, and reinforcing the use of more complex models for drug screening and a multi-approach that should include histological and ICC analysis.
Jaboticaba is a Brazilian native berry described as a rich source of phenolic compounds (PC) with health promoting effects. PC from jaboticaba peel powder (JPP) have low intestinal bio-accessibility and are catabolized by gut microbiota. However, the biological implication of PC-derived metabolites produced during JPP digestion remains unclear. This study aimed to evaluate the antiproliferative effects of colonic fermented JPP (FJPP) in a 3D model of colorectal cancer (CRC) composed by HT29 spheroids. JPP samples fermented with human feces during 0, 2, 8, 24 or 48 h were incubated (10,000 µg mL−1) with spheroids, and cell viability was assessed after 72 h. Chemometric analyses (cluster and principal component analyses) were used to identify the main compounds responsible for the bioactive effect. The antiproliferative effect of FJPP in the CRC 3D model was increased between 8 h and 24 h of incubation, and this effect was associated with HHDP-digalloylglucose isomer and dihydroxyphenyl-γ-valerolactone. At 48 h of fermentation, the antiproliferative effect of FJPP was negligible, indicating that the presence of urolithins did not improve the bioactivity of JPP. These findings provide relevant knowledge on the role of colonic microbiota fermentation to generate active phenolic metabolites from JPP with positive impact on CRC.
BackgroundBreast cancer is the most common cancer worldwide, and despite remarkable progress in its treatment, the survivors’ quality of life is hampered by treatment-related side effects that impair psychosocial and physiological outcomes. Several studies have established the benefits of physical exercise in breast cancer survivors in recent years. Physical exercise reduces the impact of treatment-related adverse events to promote a better quality of life and functional outcomes.AimThis study aims to provide an overview of systematic reviews and meta-analyses on the effect of physical exercise on the health-related quality of life, cardiorespiratory fitness, muscle strength, and body composition of breast cancer survivors.MethodsPubMed and Cochrane databases were searched for systematic reviews and meta-analyses from January 2010 to October 2022. The main focus was ascertaining the effectiveness of physical exercise in breast cancer survivors undergoing curative treatment (surgery and/or radiotherapy and/or chemotherapy). Two reviewers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies.ResultsA total of 101 studies were identified, and 12 were yielded for final analysis. The eligible studies included nine systematic reviews/meta-analyses, one meta-analysis/meta-regression, and two systematic reviews. The number of randomised clinical trials included in each review varied from 11 to 63, and the number of participants was from 214 to 5761. A positive and significant effect of different physical exercise interventions on health-related quality of life was reported in 83.3% (10 studies) of the eligible studies. Physical exercise also improved cardiorespiratory fitness (3 studies; 25%) and showed to be effective in reducing body weight (3 studies; 25%) and waist circumference (4 studies; 33.3%).ConclusionsOur results suggest that physical exercise is an effective strategy that positively affects breast cancer survivors’ quality of life, cardiorespiratory fitness, and body composition. Healthcare professionals should foster the adoption of physical exercise interventions to achieve better health outcomes following breast cancer treatments.Systematic review registrationhttps://inplasy.com/inplasy-2022-11-0053/, identifier INPLASY2022110053.
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