Reduction of cancer cell viability by synergistic combination of photodynamic treatment with the inhibition of the Id protein family

Roschger, Cornelia; Verwanger, Thomas; Krammer, Barbara; Cabrele, Chiara

doi:10.1016/j.jphotobiol.2017.11.038

Cited by 6 publications

(9 citation statements)

References 39 publications

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“…Among the resulting helical cyclopeptides, cyclo‐(2,6)‐( Ac ‐VKRLQDLQ‐ NH 2 ) ( 1 ) could nicely mimic the side‐chain hydrophobic pattern of the two ID‐protein helices at positions i, i+3, and i+6 (Figure 1A), as shown by the comparison of the NMR solution structure of 1 38 with the crystal structure of the ID2 HLH homodimer 39 . Moreover, 1Y , an analog of 1 containing an additional C‐terminal residue (Tyr‐9, used as internal chromophore) and whose NMR solution structure has been elucidated in this work (Figure 1B), was found to be an ID protein‐binding candidate that negatively modulated the cell‐cycle progression of cancer cells 38 and further achieved synergistic effects in combination with photodynamic therapy 40 …”

Section: Introductionmentioning

confidence: 62%

“…In this work, we have investigated a series of analogs of the lactam‐bridged nonapeptide 1Y , which is a ligand of the ID proteins and reduces cancer cell viability 38,40 . These analogs, which differ from 1Y in the hydrophobic pattern (residues 1, 4, 7, and 9), were found to be comparable to or less effective than 1Y in the cancer cell viability assay: In particular, the replacement of Leu‐4 with Tyr‐4 was unfavorable (Figure S9).…”

Section: Discussionmentioning

confidence: 99%

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Backbone distortions in lactam‐bridged helical peptides

Moazzam

Stanojlović

Hinterholzer

et al. 2022

Journal of Peptide Science

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Side‐chain‐to‐side‐chain cyclization is frequently used to stabilize the α‐helical conformation of short peptides. In a previous study, we incorporated a lactam bridge between the side chains of Lys‐i and Asp‐i+4 in the nonapeptide 1Y, cyclo‐(2,6)‐(Ac‐VKRLQDLQY‐NH2), an artificial ligand of the inhibitor of DNA binding and cell differentiation (ID) protein with antiproliferative activity on cancer cells. Herein, we show that only the cyclized five‐residue segment adopts a helical turn whereas the C‐terminal residues remain flexible. Moreover, we present nine 1Y analogs arising from different combinations of hydrophobic residues (leucine, isoleucine, norleucine, valine, and tyrosine) at positions 1, 4, 7, and 9. All cyclopeptides except one build a lactam‐bridged helical turn; however, residue‐4 reveals less helix character than the neighboring Arg‐3 and Gln‐5, especially with residue‐4 being isoleucine, valine, and tyrosine. Surprisingly, only two cyclopeptides exhibit helix propagation until the C‐terminus, whereas the others share a remarkable outward tilting of the backbone carbonyl of the lactam‐bridged Asp‐6 (>40° deviation from the orientation parallel to the helix axis), which prevents the formation of the H‐bond between Arg‐3 CO and residue‐7 NH: As a result, the propagation of the helix beyond the lactam‐bridged sequence becomes unfavorable. We conclude that, depending on the amino‐acid sequence, the lactam bridge between Lys‐i and Asp‐i+4 can stabilize a helical turn but deviations from the ideal helix geometry are possible: Indeed, besides the outward tilting of the backbone carbonyls, the residues per turn increased from 3.6 (typical of a regular α‐helix) to 4.2, suggesting a partial helix unwinding.

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Section: Introductionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Backbone distortions in lactam‐bridged helical peptides

Moazzam

Stanojlović

Hinterholzer

et al. 2022

Journal of Peptide Science

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“…SnP has an IC 50 value of 9.8 μM (phototoxic index > 2.1; ratio of IC 50 value in dark/light), while SnPH exhibits almost 3-fold better phototoxicity with an IC 50 value of 2.9 μM (phototoxic index > 6.9). Porphyrin-related photosensitizers that have been developed for PDT, such as Photofrin®, Foscan® and 5,10,15,20- tetrakis (4-hydroxyphenyl)porphyrin ( p -THPP), and hypericin have previously been used as positive controls in this context, 30,31 but this is now routinely omitted. 8,9,11,13 Since SnP and SnPH have similar Φ Δ values, the difference in PDT activity cells can be attributed to the higher cellular uptake observed for SnPH .…”

Section: Resultsmentioning

confidence: 99%

A Sn(iv) porphyrin with mitochondria targeting properties for enhanced photodynamic activity against MCF-7 cells

2022

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“…All cytotoxic therapies result in pro-survival treatment responses like upregulated cytokine signaling from the tumor cells that often result in failure of the primary treatment and recurrence of disease [76]. Combining remotely triggered cytotoxic agents with drugs that can tackle these pro-survival treatment responses is helping reduce therapeutic outcomes in several in vitro and in vivo models of cancer [44,75,77,78]. Our understanding of the intricacies involved in effective removal and subsequent therapeutic administration of anti-cancer drugs to GBM tumors is that nanoencapsulated drug therapy may significantly enhance BBB penetration and cancer cell targeting using reduced drug concentrations required for efficacy, as well as side effects and inadvertent damage to healthy tissue.…”

Section: Discussionmentioning

confidence: 99%

Co-Administered Polymeric Nano-Antidotes for Improved Photo-Triggered Response in Glioblastoma

2018

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Polymer-based nanoparticles (NPs) are useful vehicles in treating glioblastoma because of their favorable characteristics such as small size and ability to cross the blood–brain barrier, as well as reduced immunogenicity and side effects. The use of a photosensitizer drug such as Verteporfin (BPD), in combination with a pan-vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI), Cediranib (CED), encapsulated in NPs will provide the medical field with new research on the possible ways to treat glioblastoma. Concomitant administration of BPD and CED NPs have the potential to induce dual photocytotoxic and cytostatic effects in U87 MG cells by (1) remotely triggering BPD through photodynamic therapy by irradiating laser at 690 nm and subsequent production of reactive oxygen species and (2) inhibiting cell proliferation by VEGFR interference and growth factor signaling mechanisms which may allow for longer progression free survival in patients and fewer systemic side effects. The specific aims of this research were to synthesize, characterize and assess cell viability and drug interactions for polyethylene-glycolated (PEGylated) polymeric based CED and BPD NPs which were less than 100 nm in size for enhanced permeation and retention effects. Synergistic effects were found using the co-administered therapies compared to the individual drugs. The major goal of this research was to investigate a new combination of photodynamic-chemotherapy drugs in nano-formulation for increased efficacy in glioblastoma treatment at reduced concentrations of therapeutics for enhanced drug delivery in vitro.

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Reduction of cancer cell viability by synergistic combination of photodynamic treatment with the inhibition of the Id protein family

Cited by 6 publications

References 39 publications

Backbone distortions in lactam‐bridged helical peptides

Backbone distortions in lactam‐bridged helical peptides

A Sn(iv) porphyrin with mitochondria targeting properties for enhanced photodynamic activity against MCF-7 cells

Co-Administered Polymeric Nano-Antidotes for Improved Photo-Triggered Response in Glioblastoma

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