scholarly journals Bystander Effects of Nitric Oxide in Cellular Models of Anti-Tumor Photodynamic Therapy

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1674 ◽  
Author(s):  
Jerzy Bazak ◽  
Witold Korytowski ◽  
Albert W. Girotti

Tumor cells exposed to stress-inducing radiotherapy or chemotherapy can send signals to non- or minimally exposed bystander cells. Bystander effects of ionizing radiation are well established, but little is known about such effects in non-ionizing photodynamic therapy (PDT). Our previous studies revealed that several cancer cell types upregulate inducible nitric oxide synthase (iNOS) and nitric oxide (NO) after a moderate 5-aminolevulinic acid (ALA)-based PDT challenge. The NO signaled for cell resistance to photokilling as well as greater growth, migration and invasion of surviving cells. Based on this work, we hypothesized that diffusible NO produced by PDT-targeted cells in a tumor might elicit pro-growth/migration responses in non-targeted bystander cells. In the present study, we tested this using a novel approach, in which ALA-PDT-targeted human cancer cells on culture dishes (prostate PC3, breast MDA-MB-231, glioma U87, or melanoma BLM) were initially segregated from non-targeted bystanders via impermeable silicone-rimmed rings. Several hours after LED irradiation, rings were removed, and both cell populations analyzed for various post-hν responses. For a moderate and uniform level of targeted cell killing by PDT (~25%), bystander proliferation and migration were both enhanced. Enhancement correlated with iNOS/NO upregulation in surviving targeted cells in the following order: PC3 > MDA-MB-231 > U87 > BLM. If occurring in an actual tumor PDT setting and not suppressed (e.g., by iNOS activity or transcription inhibitors), then such effects could compromise treatment efficacy or even stimulate disease progression if PDT’s anti-tumor potency is not great enough.

2021 ◽  
Vol 14 (3) ◽  
pp. 229
Author(s):  
Yo Shinoda ◽  
Daitetsu Kato ◽  
Ryosuke Ando ◽  
Hikaru Endo ◽  
Tsutomu Takahashi ◽  
...  

5-Aminolevulinic acid (5-ALA) is an amino acid derivative and a precursor of protoporphyrin IX (PpIX). The photophysical feature of PpIX is clinically used in photodynamic diagnosis (PDD) and photodynamic therapy (PDT). These clinical applications are potentially based on in vitro cell culture experiments. Thus, conducting a systematic review and meta-analysis of in vitro 5-ALA PDT experiments is meaningful and may provide opportunities to consider future perspectives in this field. We conducted a systematic literature search in PubMed to summarize the in vitro 5-ALA PDT experiments and calculated the effectiveness of 5-ALA PDT for several cancer cell types. In total, 412 articles were identified, and 77 were extracted based on our inclusion criteria. The calculated effectiveness of 5-ALA PDT was statistically analyzed, which revealed a tendency of cancer-classification-dependent sensitivity to 5-ALA PDT, and stomach cancer was significantly more sensitive to 5-ALA PDT compared with cancers of different origins. Based on our analysis, we suggest a standardized in vitro experimental protocol for 5-ALA PDT.


2014 ◽  
Vol 157 (4) ◽  
pp. 476-478 ◽  
Author(s):  
A. V. Snigireva ◽  
V. V. Vrublevskaya ◽  
Yu. Yu. Skarga ◽  
Yu. V. Evdokimovskaya ◽  
O. S. Morenkov

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5590
Author(s):  
Gilberto Jaramillo-Rangel ◽  
María-de-Lourdes Chávez-Briones ◽  
Alberto Niderhauser-García ◽  
Marta Ortega-Martínez

Karwinskia genus consists of shrubs and small trees. Four toxic compounds have been isolated from Karwinskia plants, which were typified as dimeric anthracenones and named T496, T514, T516, and T544. Moreover, several related compounds have been isolated and characterized. Here we review the toxicity of the fruit of Karwinskia plants when ingested (accidentally or experimentally), as well as the toxicity of its isolated compounds. Additionally, we analyze the probable antineoplastic effect of T514. Toxins cause damage mainly to nervous system, liver, lung, and kidney. The pathophysiological mechanism has not been fully understood but includes metabolic and structural alterations that can lead cells to apoptosis or necrosis. T514 has shown selective toxicity in vitro against human cancer cells. T514 causes selective and irreversible damage to peroxisomes; for this reason, it was renamed peroxisomicine A1 (PA1). Since a significant number of malignant cell types contain fewer peroxisomes than normal cells, tumor cells would be more easily destroyed by PA1 than healthy cells. Inhibition of topoisomerase II has also been suggested to play a role in the effect of PA1 on malignant cells. More research is needed, but the evidence obtained so far indicates that PA1 could be an effective anticancer agent.


2019 ◽  
Vol 9 ◽  
Author(s):  
Na Guo ◽  
Ge Shen ◽  
Ying Zhang ◽  
Ahmed A. Moustafa ◽  
Dongxia Ge ◽  
...  

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 701 ◽  
Author(s):  
Patryk Bil ◽  
Sylwia Ciesielska ◽  
Roman Jaksik ◽  
Joanna Rzeszowska-Wolny

Superoxide radicals, together with nitric oxide (NO), determine the oxidative status of cells, which use different pathways to control their levels in response to stressing conditions. Using gene expression data available in the Cancer Cell Line Encyclopedia and microarray results, we compared the expression of genes engaged in pathways controlling reactive oxygen species and NO production, neutralization, and changes in response to the exposure of cells to ionizing radiation (IR) in human cancer cell lines originating from different tissues. The expression of NADPH oxidases and NO synthases that participate in superoxide radical and NO production was low in all cell types. Superoxide dismutase, glutathione peroxidase, thioredoxin, and peroxiredoxins participating in radical neutralization showed high expression in nearly all cell types. Some enzymes that may indirectly influence superoxide radical and NO levels showed tissue-specific expression and differences in response to IR. Using fluorescence microscopy and specific dyes, we followed the levels and the distribution of superoxide and NO radicals in living melanoma cells at different times after exposure to IR. Directly after irradiation, we observed an increase of superoxide radicals and NO coexistent in the same subcellular locations, suggesting a switch of NO synthase to the production of superoxide radicals.


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