Contextualisation of the new type of cell death called “ferroptosis” opened a completely new avenue for the development of anti-cancer therapies. Cumulative fundamental research dating back to the mid-20th century, crowned by the extraordinary work of the group led by Dr. Stockwell from Columbia University in 2012, finally got its candidature to be applied in the clinical settings. Although the potential for clinical importance is undoubtedly growing every day, as showed by the increasing number of papers dealing with ferroptosis and its applications, long experience of cancer research and treatment taught us that caution is still necessary. The plasticity of the tumour cells, particularly acute, along with its involvement in the resistance mechanisms, that have been seen, to greater or lesser extent, for almost all currently used therapies, represents the biggest fascinations in biomedical research field and also the biggest challenge to achieving cures in cancer patients. Accordingly, the main features of fundamental research have to be vigilance and anticipation. In this review, we tried to summarize the literature data, accumulated in the past couple of years, which point out the pitfalls in which “ferroptosis inducers” can fall if used prematurely in the clinical settings, but at the same time can provide a great advantage in the exhausting battle with cancer resistance. This is the first comprehensive review focusing on the effects of the cell-to-cell contact/interplay in the development of resistance to ferroptosis, while the contribution of cell-born factors has been summarized previously so here we just listed them.
In our previous study, we showed that a cystine transporter (xCT) plays a pivotal role in ferroptosis of pancreatic ductal adenocarcinoma (PDAC) cells in vitro. However, in vivo xCTKO cells grew normally indicating that a mechanism exists to drastically suppress the ferroptotic phenotype. We hypothesized that plasma and neighboring cells within the tumor mass provide a source of cysteine to confer full ferroptosis resistance to xCTKO PDAC cells. To evaluate this hypothesis, we (co-) cultured xCTKO PDAC cells with different xCT-proficient cells or with their conditioned media. Our data unequivocally showed that the presence of a cysteine/cystine shuttle between neighboring cells is the mechanism that provides redox and nutrient balance, and thus ferroptotic resistance in xCTKO cells. Interestingly, although a glutathione shuttle between cells represents a good alternative hypothesis as a “rescue-mechanism”, our data clearly demonstrated that the xCTKO phenotype is suppressed even with conditioned media from cells lacking the glutathione biosynthesis enzyme. Furthermore, we demonstrated that prevention of lipid hydroperoxide accumulation in vivo is mediated by import of cysteine into xCTKO cells via several genetically and pharmacologically identified transporters (ASCT1, ASCT2, LAT1, SNATs). Collectively, these data highlight the importance of the tumor environment in the ferroptosis sensitivity of cancer cells.
Resumo. Foi realizada uma análise comparativa com base na morfologia detalhada do exoesqueleto e genitália do adulto de oito espécies de Coccinellini: Coleomegilla quadrifasciata (Schönherr, 1808); Cycloneda sanguinea (Linnaeus, 1763); Cycloneda pulchella (Klug, 1829); Eriopis connexa (Germar, 1824); Harmonia axyridis (Pallas, 1773); Hippodamia convergens (Guérin, 1842); Neocalvia anastomozans (Crotch, 1874); Olla v-nigrum (Mulsant, 1866). É apresentado uma chave de identificação, diagnose para cada espécie com a descrição de novos caracteres, além do registro das plantas nas quais foram coletadas.
Palavras-chave:Chave de identificação; Controle biológico; Redescrição; Taxonomia.
Morphology of the Coccinellini (Coleoptera, Coccinellidae) deposited in the Coleção Entomológica dos Campos Gerais do
Melanoma is a type of tumor that originates from melanocytes. Irradiation of melanin with UVA and visible light can produce reactive oxygen species (ROS) such as singlet molecular oxygen ( 1 O 2 ). The objective of this study was to examine DNA damage in melanoma cells (B16-F10) with different melanin contents, subjected to 1 O 2 generation. To this end, we used the photosensitizer Rose Bengal acetate (RBAc) and irradiation with visible light (526 nm) (RBAc-PDT). We used the modified comet assay with the repair enzymes hOGG1 and T4 endonuclease V to detect the DNA damage associated with 8-oxo-7,8-dihydro-2 0 -deoxyguanosine and cyclobutane pyrimidine dimers lesions, respectively. We observed increased formation of hOGG1-and T4endoV-sensitive DNA lesions after light exposure (with or without RBAc). Furthermore, 18 h after irradiation, hOGG1-sensitive DNA lesions increased compared to that at the initial time point (0 h), which shows that a high melanin content contributes to post-irradiation formation of them, mainly via sustained oxidative stress, as confirmed by the measurement of ROS levels and activity of antioxidant enzymes. Contrastingly, the number of T4endoVsensitive DNA lesions decreased over time (18 h). Our data indicate that in melanoma cells, a higher amount of melanin may affect DNA damage levels when subjected to RBAc-PDT.
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