scholarly journals The Assessment of the Combined Treatment of 5-ALA Mediated Photodynamic Therapy and Thalidomide on 4T1 Breast Carcinoma and 2H11 Endothelial Cell Line

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5184
Author(s):  
Krzysztof Zduniak ◽  
Katarzyna Gdesz-Birula ◽  
Marta Woźniak ◽  
Kamila Duś-Szachniewicz ◽  
Piotr Ziółkowski

Photodynamic therapy (PDT) is a low-invasive method of treatment of various diseases, mainly neoplastic conditions. PDT has been experimentally combined with multiple treatment methods. In this study, we tested a combination of 5-aminolevulinic acid (5-ALA) mediated PDT with thalidomide (TMD), which is a drug presently used in the treatment of plasma cell myeloma. TMD and PDT share similar modes of action in neoplastic conditions. Using 4T1 murine breast carcinoma and 2H11 murine endothelial cells lines as an experimental tumor model, we tested 5-ALA-PDT and TMD combination in terms of cytotoxicity, apoptosis, Vascular Endothelial Growth Factor (VEGF) expression, and, in 2H11 cells, migration capabilities by wound healing assay. We have found an enhancement of cytotoxicity in 4T1 cells, whereas, in normal 2H11 cells, this effect was not statistically significant. The addition of TMD decreased the production of VEGF after PDT in 2H11 cell line. Our results reveal enhanced effectiveness of 5-ALA-PDT with TMD treatment compared to 5-ALA-PDT or TMD treatment alone. The addition of TMD may be a promising proceeding of the anti-tumor effect of PDT by decreasing the VEGF concentration in the culture medium. Further studies, including testing on different cell lines, are needed to confirm this assumption.

2017 ◽  
Vol 20 ◽  
pp. 111-115 ◽  
Author(s):  
Jan F. Cornelius ◽  
Lennert Eismann ◽  
Lara Ebbert ◽  
Brigitte Senger ◽  
Athanasios K. Petridis ◽  
...  

2009 ◽  
Vol 6 (12) ◽  
pp. 886-891 ◽  
Author(s):  
M. Atif ◽  
S. Firdous ◽  
A. Khurshid ◽  
L. Noreen ◽  
S.S.Z. Zaidi ◽  
...  

2019 ◽  
Vol 121 (9) ◽  
pp. 758-767 ◽  
Author(s):  
Vipin Shankar Chelakkot ◽  
Jayoti Som ◽  
Ema Yoshioka ◽  
Chantel P. Rice ◽  
Suzette G. Rutihinda ◽  
...  

Abstract Background Protoporphyrin IX (PpIX) gets accumulated preferentially in 5-aminolevulinic acid (5-ALA)-treated cancer cells. Photodynamic therapy (PDT) utilises the accumulated PpIX to trigger cell death by light-induced generation of reactive oxygen species (ROS). We previously demonstrated that oncogenic Ras/MEK decreases PpIX accumulation in cancer cells. Here, we investigated whether combined therapy with a MEK inhibitor would improve 5-ALA-PDT efficacy. Methods Cancer cells and mice models of cancer were treated with 5-ALA-PDT, MEK inhibitor or both MEK inhibitor and 5-ALA-PDT, and treatment efficacies were evaluated. Results Ras/MEK negatively regulates the cellular sensitivity to 5-ALA-PDT as cancer cells pre-treated with a MEK inhibitor were killed more efficiently by 5-ALA-PDT. MEK inhibition promoted 5-ALA-PDT-induced ROS generation and programmed cell death. Furthermore, the combination of 5-ALA-PDT and a systemic MEK inhibitor significantly suppressed tumour growth compared with either monotherapy in mouse models of cancer. Remarkably, 44% of mice bearing human colon tumours showed a complete response with the combined treatment. Conclusion We demonstrate a novel strategy to promote 5-ALA-PDT efficacy by targeting a cell signalling pathway regulating its sensitivity. This preclinical study provides a strong basis for utilising MEK inhibitors, which are approved for treating cancers, to enhance 5-ALA-PDT efficacy in the clinic.


2008 ◽  
Author(s):  
Aleksandra Kawczyk-Krupka ◽  
Zenon Czuba ◽  
Aleksandra Ledwon ◽  
Wojciech Latos ◽  
Ewelina Sliszka ◽  
...  

2006 ◽  
Vol 82 (6) ◽  
pp. 1638 ◽  
Author(s):  
Ingrid A. Boere ◽  
Dominic J. Robinson ◽  
Henriette S. de Bruijn ◽  
Jolanda Kluin ◽  
Hugo W. Tilanus ◽  
...  

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