Inhibition of MAPK signaling pathways enhances cell death induced by 5-Aminolevulinic acid-photodynamic therapy in skin squamous carcinoma cells

2016 ◽  
Vol 26 (2) ◽  
pp. 164-172 ◽  
Author(s):  
Xinhong Ge ◽  
Jianping Liu ◽  
Zhiyun Shi ◽  
Li Jing ◽  
Nan Yu ◽  
...  
Author(s):  
Anette Magnussen ◽  
Charlotte Reburn ◽  
Alexis Perry ◽  
Mark Wood ◽  
Alison Curnow

AbstractPhotodynamic therapy (PDT) is an oxygen-dependent, light-activated, and locally destructive drug treatment of cancer. Protoporphyrin IX (PpIX)-induced PDT exploits cancer cells’ own innate heme biosynthesis to hyper-accumulate the naturally fluorescent and photoactive precursor to heme, PpIX. This occurs as a result of administering heme precursors (e.g., aminolevulinic acid; ALA) because the final step of the pathway (the insertion of ferrous iron into PpIX by ferrochelatase to form heme) is relatively slow. Separate administration of an iron chelating agent has previously been demonstrated to significantly improve dermatological PpIX-PDT by further limiting heme production. A newly synthesized combinational iron chelating PpIX prodrug (AP2-18) has been assessed experimentally in cultured primary human cells of bladder and dermatological origin, as an alternative photosensitizing agent to ALA or its methyl or hexyl esters (MAL and HAL respectively) for photodetection/PDT. Findings indicated that the technique of iron chelation (either through the separate administration of the established hydroxypyridinone iron chelator CP94 or the just as effective combined AP2-18) did not enhance either PpIX fluorescence or PDT-induced (neutral red assessed) cell death in human primary normal and malignant bladder cells. However, 500 µM AP2-18 significantly increased PpIX accumulation and produced a trend of increased cell death within epithelial squamous carcinoma cells. PpIX accumulation destabilized the actin cytoskeleton in bladder cancer cells prior to PDT and resulted in caspase-3 cleavage/early apoptosis afterwards. AP2-18 iron chelation should continue to be investigated for the enhancement of dermatological PpIX-PDT applications but not bladder photodetection/PDT.


2021 ◽  
Vol 11 (8) ◽  
pp. 3524
Author(s):  
Azeem Ul Yaqin Syed ◽  
Muhammad A. Ahmed ◽  
Eman I. AlSagob ◽  
Mansour Al-Askar ◽  
Abdulrahman M. AlMubarak ◽  
...  

The aim was to determine the cytotoxicity of Khat (Catha edulis (Vahl) Forssk. ex Endl) on normal oral fibroblasts (NOFs) and SCC4 (squamous carcinoma cells) along with expression of α-smooth muscle actin (α-SMA) in fibroblasts. Khat filtrate was prepared to obtain a concentrated viscous solution. NOFs and SCC4 cells were cultured in biological cabinets and were grown in Dulbeccos’ modified Eagles medium. Frozen cells were thawed at 37 °C and cell seeding was performed. NOFs and SCC4 cells were seeded on 96 well plates and allowed to attach. The medium was removed and a fresh medium containing different concentrations of Khat was added. The group without Khat served as a negative control and 4% paraformaldehyde as the positive control. Cell viability was assessed using the MTT assay and effect of Khat on fibroblast and SCC4 phenotypes was evaluated by immunostaining. Analysis of variance was used to assess data (p < 0.05). NOF 316 showed cell death in response to 4% paraformaldehyde, 12.5, 6.25, and 3.12 mg/mL of Khat. The highest concentration of Khat (25 mg/mL) failed to cause cytotoxicity of NOF 316. NOF 319 and NOF 26 displayed cell death at all concentrations of Khat, however, cytotoxicity was not dose dependent. NOF 18 and SCC4 cells showed dose-dependent cell death. NOF 316 showed α-SMA expression after 1 mg/mL of Khat exposure. Not all fibroblasts were α-SMA-positive, suggesting specific activation of a subset of fibroblasts. Khat is cytotoxic to NOF and SCC4 cells. Furthermore, it can also cause activation and phenotypic changes in oral fibroblasts, indicating a potential role in progression of oral squamous cell carcinoma.


2012 ◽  
Vol 13 (3) ◽  
pp. NP18-NP28 ◽  
Author(s):  
Kuei-Li Lin ◽  
Ching-Ming Chien ◽  
Chih-Hua Tseng ◽  
Yeh-Long Chen ◽  
Long-Sen Chang ◽  
...  

2012 ◽  
Vol 288 (1) ◽  
pp. 677-686 ◽  
Author(s):  
Hsin-I Hung ◽  
Justin M. Schwartz ◽  
Eduardo N. Maldonado ◽  
John J. Lemasters ◽  
Anna-Liisa Nieminen

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