Browsing by Author "Monteiro, Armanda"
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- Adipocyte secretome increases radioresistance of malignant melanocytes by improving cell survival and decreasing oxidative statusPublication . Coelho, Pedro; Silva, Liliana; Faria, Isabel; Vieira, Mónica; Monteiro, Armanda; Pinto, Gabriela; Prudêncio, Cristina; Fernandes, Rúben; Soares, RaquelRadiotherapy is a treatment option for the majority of malignancies. However, because melanoma is known to be radioresistant, the use of ionizing radiation as an adjuvant therapy in cutaneous melanoma patients is ineffective. Obesity has now been recognized as a risk factor for melanoma. High adiposity is generally associated with a more pro-oxidative status. Oxidative stress is a major player in radiation therapy and also a common link between obesity and cancer. Several adipocyte-released proteins are known to have a role in controlling cellular growth and pro-survival signaling. For that reason, we investigated the influence of 3T3-L1 mature adipocyte secretome in B16-F10 malignant melanocyte radiosensitivity. We evaluated B16-F10 cell survival and redox homeostasis when exposed to four daily doses of ionizing radiation (2 Gy per day) up to a total of 8 Gy in a medical linear accelerator. B16-F10 melanocytes exhibited slight alterations in survival, catalase activity, nitrative stress and total oxidant concentration after the first 2 Gy irradiation. The motility of the melanocytes was also delayed by ionizing radiation. Subsequent irradiations of the malignant melanocytes led to more prominent reductions in overall survival. Remarkably, 3T3-L1 adipocyte-secreted molecules were able to increase the viability and migration of melanocytes, as well as lessen the pro-oxidant burden induced by both the single and cumulative X-ray doses. In vitro adipocyte-released factors protected B16-F10 malignant melanocytes from both oxidative stress and loss of viability triggered by radiation, enhancing the radioresistant phenoyype of these cells with a concomitant activation of the AKT signaling pathway These results both help to elucidate how obesity influences melanoma radioresistance and support the usage of conventional medical linear accelerators as a valid model for the in vitro radiobiological study of tumor cell lines.
- Application of gold nanoparticles as radiosensitizer for metastatic prostate cancer cell linesPublication . Soares, Sílvia; Faria, Isabel; Aires, Fátima; Monteiro, Armanda; Pinto, Gabriela; Sales, Maria Goreti; Correa-Duarte, Miguel A.; Guerreiro, Susana G.; Fernandes, RúbenMore than 50% of all prostate cancer (PCa) patients are treated by radiotherapy (RT). Radioresistance and cancer recurrence are two consequences of the therapy and are related to dose heterogeneity and non-selectivity between normal and tumoral cells. Gold nanoparticles (AuNPs) could be used as potential radiosensitizers to overcome these therapeutic limitations of RT. This study assessed the biological interaction of different morphologies of AuNPs with ionizing radiation (IR) in PCa cells. To achieve that aim, three different amine-pegylated AuNPs were synthesized with distinct sizes and shapes (spherical, AuNPsp-PEG, star, AuNPst-PEG, and rods, AuNPr-PEG) and viability, injury and colony assays were used to analyze their biological effect on PCa cells (PC3, DU145, and LNCaP) when submitted to the accumulative fraction of RT. The combinatory effect of AuNPs with IR decreased cell viability and increased apoptosis compared to cells treated only with IR or untreated cells. Additionally, our results showed an increase in the sensitization enhancement ratio by cells treated with AuNPs and IR, and this effect is cell line dependent. Our findings support that the design of AuNPs modulated their cellular behavior and suggested that AuNPs could improve the RT efficacy in PCa cells.
- Biomolecules in the relationship of cancer and obesityPublication . Almeida, Joana; Coelho, Pedro; Prudêncio, Cristina; Vieira, Mónica; Fernandes, Rúben; Fonseca, Magda; Soares, Raquel; Silva, Liliana; Faria, Isabel; Monteiro, Armanda; Pinto, Gabriela; Cea, V.; Galesio, M.; Noronha, J. P.; Diniz, M. S.; Sala, C.Obesity has been associated with various major causes of death and morbidity including malignant neoplasms. This increased prevalence has been accompanied by a worldwide increase in cutaneous melanoma incidence rates during the last decades, as well as gliomas, the most common primary malignant brain tumors in adults (Almeida et al., 2019). Although obesity aetiology is established, the implicated mechanisms remain unclear (Coelho et al., 2016). Melanoma is refractory to conventional therapies, and radiotherapy usage as an adjuvant therapy in cutaneous melanoma patients is ineffective, so it is extremely important to understand the antioxidant modulation of melanoma under an environment of obesity (Coelho et al., 2017; Oliveira et al., 2016). Moreover, the metastatic potential of some types of cancer is reduced or inhibited by obesity, which drives major concerns on the prognosis of metastasized patients (Fonseca et al., 2021). All of the studies disclose interesting models for the study of these tumors’ biology under an obese environment, that can be explored for the search of biomarkers, prognostic markers and therapeutic approaches.
- Oxidative Stress Modulation and Radiosensitizing Effect of Quinoxaline-1,4-Dioxides DerivativesPublication . Silva, Liliana; Coelho, Pedro; Teixeira, Dulce; Monteiro, Armanda; Pinto, Gabriela; Soares, Raquel; Prudêncio, Cristina; Vieira, MónicaQuinoxaline-1,4-dioxide (QNX) derivatives are synthetic heterocyclic compounds with multiple biological and pharmacological effects. In this study, we investigated the oxidative status of quinoxaline-1,4-dioxides derivatives in modulating melanoma and glioma cell lines, based on previous results from the research group and their capability to promote cell damage by the production of Reactive Oxygen Species (ROS).
- Potentional radiosensitizer effect of TUDCA in a obesity model of brain tumor cellsPublication . Silva, Liliana; Almeida, Joana; Coelho, Pedro; Faria, Isabel; Monteiro, Armanda; Soares, Raquel; Vieira, Mónica; Prudêncio, Cristina; Fernandes, RúbenObesity may play an important role in the biology of seve ral types of cancer, but the correlation with glioma Is still not very well defined. Former studies indicated that obesity may be related with an decreased resistance to radiation and increased redox status in brain tumors. Since radiothetapy is the most commonly treatment modality used in this type of tumor, we creale a new model of experiments to determinate the influence of obesity in glioma cells [n the presence of radiation with an imbalance of redox status, BC3H1 glioma cells were treated with t-BOOH (150~M), TUDCA (25~M) and a mix of t-BOOH and TUOCA{150~M and 25~M respectively) in serum-free OMEM or conditioned media (CM) from differentiated 3T3-L 1 adj pocytes. Afterwards the cells were irradiated with a total dose of 2 Gy. Subsequently BC3H1 viability was evaluated, by MTT assay, after 4 and 12 hours. We observed an increase in viability In all cells treated solely with 3T3-L 1 eM. Interestingly, in the presence of CM plus TUDCA or t-BOOH, the viability of 6C3H1 was inferior of TUOCA or t~BOOH treatments alone, this effect was independent of irradia tion. After 12 hours the I/iability of the glioma cells was significantly higher on irradiated ceUs treated only with eM, this effect was not yet observed at the 4 hours time point But, in the presence of mix of t~BOOH and TUDCA, with eM and irradiation the cells viability decrea se significanUy. The 3T3-L 1 Me increase (he cell viabrlity in the presence of radiation or not, after 12 hours expose" But in the presence of oxidatIve inducer and, In specially, with the antioxidant TUDCA, the BC3Hi viability significantly decrease. So, we observed a potential radiosensitfzer effect of TUDCA in BC3H1 in the presence of 3T3-L1 adipocytes.