Abstract:Objective
Osteosarcoma (OS) is characterized by high levels of the tumour‐associated inflammatory microenvironment. Moreover, in approximately 60% of OS, telomere length is maintained by alternative lengthening of telomeres (ALT) pathway. Whether the ALT pathway can be exploited for OS therapeutic treatment and how the OS inflammatory microenvironment influences the anti‐cancer drug effect remains unknown. Here, we examined the biological effects of TMPyP4 and cisplatin in the inflammatory microenvironment of … Show more
“…In turn, TMPyP4, a porphyrins derivative, is a quadruplex-specific ligand. It stabilizes G-quadruplex helices and inhibits the activity of the enzyme telomerase, which is overexpressed in >80% of cancer cells [ 21 , 48 ]. TMPyP4 also significantly reduced the integrin beta-1-mediated pathway [ 49 ].…”
Section: Discussionmentioning
confidence: 99%
“…In turn, 5,10,15,20-Tetrakis (1-methyl-4-pyridinio) porphyrin is reported to be a promising photodynamic therapy photosensitizer. Moreover, it is one of the most studied G-quadruplex porphyrin ligands, used as a model to show that ligands can exhibit different binding features with different conformations of a human telomeric specific sequence [ 21 ]. However, the effects of both porphyrins have not been investigated on cell migration in a human colon tumor and normal cell cultures in the context of the effect of white light irradiation.…”
Standard therapies for colorectal cancer cannot eliminate or sufficiently reduce the metastasis process. Photodynamic therapy (PDT) may be an alternative to minimizing this problem. Here, we examined the cellular localization of selected porphyrins and determined whether free-base and manganese (III) metallated porphyrins may limit colon cancer cells’ (HT29) or normal colon epithelial cells’ (CCD 841 CoTr) motility in vitro. White light irradiation was used to initiate the photodynamic effect. Porphyrin uptake by the cells was determined by porphyrin fluorescence measurements through the use of confocal microscopy. Free-base porphyrin was found in cells, where it initially localized at the edge of the cytoplasm and later in the perinuclear area. The concentrations of porphyrins had no effect on cancer cell migration but had a significant effect on normal cell motility. Due to the low concentrations of porphyrins used, no changes in F-actin filaments of the cellular cytoskeleton were detected. Signal transmission via connexons between neighbouring cells was limited to a maximum of 40 µm for HT29 and 30 µm for CCD 841 CoTr cells. The tested porphyrins differed in their activity against the tumor and normal cells’ migration capacity. Depending on the porphyrin used and the type of cells, their migration changed in relation to the control sample. The use of white light may change the activity of the porphyrins relative to the migratory capacity of the cells. The aim of the present study was to analyse the intracellular localization of tested porphyrins and their influence on the mobility of cells after irradiation with harmless white light.
“…In turn, TMPyP4, a porphyrins derivative, is a quadruplex-specific ligand. It stabilizes G-quadruplex helices and inhibits the activity of the enzyme telomerase, which is overexpressed in >80% of cancer cells [ 21 , 48 ]. TMPyP4 also significantly reduced the integrin beta-1-mediated pathway [ 49 ].…”
Section: Discussionmentioning
confidence: 99%
“…In turn, 5,10,15,20-Tetrakis (1-methyl-4-pyridinio) porphyrin is reported to be a promising photodynamic therapy photosensitizer. Moreover, it is one of the most studied G-quadruplex porphyrin ligands, used as a model to show that ligands can exhibit different binding features with different conformations of a human telomeric specific sequence [ 21 ]. However, the effects of both porphyrins have not been investigated on cell migration in a human colon tumor and normal cell cultures in the context of the effect of white light irradiation.…”
Standard therapies for colorectal cancer cannot eliminate or sufficiently reduce the metastasis process. Photodynamic therapy (PDT) may be an alternative to minimizing this problem. Here, we examined the cellular localization of selected porphyrins and determined whether free-base and manganese (III) metallated porphyrins may limit colon cancer cells’ (HT29) or normal colon epithelial cells’ (CCD 841 CoTr) motility in vitro. White light irradiation was used to initiate the photodynamic effect. Porphyrin uptake by the cells was determined by porphyrin fluorescence measurements through the use of confocal microscopy. Free-base porphyrin was found in cells, where it initially localized at the edge of the cytoplasm and later in the perinuclear area. The concentrations of porphyrins had no effect on cancer cell migration but had a significant effect on normal cell motility. Due to the low concentrations of porphyrins used, no changes in F-actin filaments of the cellular cytoskeleton were detected. Signal transmission via connexons between neighbouring cells was limited to a maximum of 40 µm for HT29 and 30 µm for CCD 841 CoTr cells. The tested porphyrins differed in their activity against the tumor and normal cells’ migration capacity. Depending on the porphyrin used and the type of cells, their migration changed in relation to the control sample. The use of white light may change the activity of the porphyrins relative to the migratory capacity of the cells. The aim of the present study was to analyse the intracellular localization of tested porphyrins and their influence on the mobility of cells after irradiation with harmless white light.
“…However, the G-quadruplex regulation in cancer still remains unsolved problems. Many G-quadruplex ligands don’t exhibit selectivity between different G-quadruplexes ( Chen J. et al, 2021 ; Galati et al, 2021 ), generating potential side effects or low efficiency. The binding affinity of some ligands still needs to be improved ( Kosiol et al, 2021 ) to benefit clinical usage.…”
Ferroptosis is a novel form of regulated cell death trigged by various biological processes, and p53 is involved in different ferroptosis regulations and functions as a crucial regulator. Both DNA and RNA can fold into G-quadruplex in GC-rich regions and increasing shreds of evidence demonstrate that G-quadruplexes have been associated with some important cellular events. Investigation of G-quadruplexes is thus vital to revealing their biological functions. Specific G-quadruplexes are investigated to discover new effective anticancer drugs. Multiple modulations have been discovered between the secondary structure G-quadruplex and p53, probably further influencing the ferroptosis in cancer. G-quadruplex binds to ferric iron-related structures directly and may affect the p53 pathways as well as ferroptosis in cancer. In addition, G-quadruplex also interacts with p53 indirectly, including iron-sulfur cluster metabolism, telomere homeostasis, lipid peroxidation, and glycolysis. In this review, we summarized the latent interplay between G-quadruplex and p53 which focused mainly on ferroptosis in cancer to provide the potential understanding and encourage future studies.
“…(Table 1 ). Especially, PDS, Braco-19, and TMPyP4 have been widely used to explore potential mechanism associated with G4 in aging-related diseases, metabolic diseases, and antiviral therapy [ 39 , 44 , 51 – 53 ]. Fig.…”
Section: Structural and Functional Characteristics Of G4mentioning
The excessive production of reactive oxygen species (ROS) can lead to single nucleic acid base damage, DNA strand breakage, inter- and intra-strand cross-linking of nucleic acids, and protein-DNA cross-linking involved in the pathogenesis of cancer, neurodegenerative diseases, and aging. G-quadruplex (G4) is a stacked nucleic acid structure that is ubiquitous across regulatory regions of multiple genes. Abnormal formation and destruction of G4s due to multiple factors, including cations, helicases, transcription factors (TFs), G4-binding proteins, and epigenetic modifications, affect gene replication, transcription, translation, and epigenetic regulation. Due to the lower redox potential of G-rich sequences and unique structural characteristics, G4s are highly susceptible to oxidative damage. Additionally, the formation, stability, and biological regulatory role of G4s are affected by ROS. G4s are involved in regulating gene transcription, translation, and telomere length maintenance, and are therefore key players in age-related degeneration. Furthermore, G4s also mediate the antioxidant process by forming stress granules and activating Nrf2, which is suggestive of their involvement in developing ROS-related diseases. In this review, we have summarized the crosstalk between ROS and G4s, and the possible regulatory mechanisms through which G4s play roles in aging and age-related diseases.
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