scholarly journals Antimalarial Drugs Enhance the Cytotoxicity of 5-Aminolevulinic Acid-Based Photodynamic Therapy against the Mammary Tumor Cells of Mice In Vitro

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3891 ◽  
Author(s):  
Tomohiro Osaki ◽  
Kiwamu Takahashi ◽  
Masahiro Ishizuka ◽  
Tohru Tanaka ◽  
Yoshiharu Okamoto

Artemisinin and its derivatives, including artesunate (ART) and artemether (ARM), exert anticancer effects in the micromolar range in drug and radiation-resistant cell lines. Artemisinin has been reported to sensitize cervical cancer cells to radiotherapy. In the present study, we determined whether ART and ARM could enhance the cytotoxicity of 5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT) against the mammary tumor cells of mice. The corrected PpIX fluorescence intensities in the control, 5-ALA, 5-ALA + ART, and 5-ALA + ARM groups were 3.385 ± 3.730, 165.7 ± 33.45, 139.0 ± 52.77, and 165.4 ± 51.10 a.u., respectively. At light doses of 3 and 5 J/cm2, the viability of 5-ALA-PDT-treated cells significantly decreased with ART (p < 0.01 and p < 0.01) and ARM treatment (p < 0.01 and p < 0.01). Besides, the number of annexin V-FITC and ethidium homodimer III-positive cells was greater in the 5-ALA-PDT with ARM group than that in the other groups. N-acetylcysteine could not significantly inhibit the percentages of apoptotic cells or inviable cells induced by 5-ALA-PDT with ARM. These reactive oxygen species-independent mechanisms might enhance cytotoxicity in 5-ALA-PDT with ARM-treated tumor cells, suggesting that the use of 5-ALA-PDT with ARM could be a new strategy to enhance PDT cytotoxicity against tumor cells. However, as these results are only based on in vitro studies, further in vivo investigations are required.

2017 ◽  
Vol 79 (6) ◽  
pp. 1195-1203 ◽  
Author(s):  
Elham Mousavi ◽  
Shahrzad Tavakolfar ◽  
Ali Almasirad ◽  
Zahra Kooshafar ◽  
Soudeh Dehghani ◽  
...  

Molecules ◽  
2017 ◽  
Vol 22 (4) ◽  
pp. 533 ◽  
Author(s):  
Tomohiro Osaki ◽  
Yoshihiro Uto ◽  
Masahiro Ishizuka ◽  
Tohru Tanaka ◽  
Nobuyasu Yamanaka ◽  
...  

2018 ◽  
Vol 201 ◽  
pp. 280-292 ◽  
Author(s):  
Eliana Rezende Adami ◽  
Claudia Rita Corso ◽  
Natalia Mulinari Turin-Oliveira ◽  
Claudia Martins Galindo ◽  
Letícia Milani ◽  
...  

Author(s):  
Beata Osiecka ◽  
Kamil Jurczyszyn ◽  
Krzysztof Symonowicz ◽  
Andrzej Bronowicz ◽  
Paweł Ostasiewicz ◽  
...  

AbstractPhotodynamic therapy (PDT) is a well-known method for the treatment of malignant tumors, and its principles have been well established over the past 30 years. This therapy involves the application of a chemical called a photosensitizer and its subsequent excitation with light at the appropriate wavelength and energy. Topical photodynamic therapy with aminolevulinic acid (5-ALA) is an alternative therapy for many malignant processes, including nonmelanoma skin cancers such as basal-cell carcinoma (BCC). Our novel approach for this study was to use a liposomal formulation of 5-ALA and its methyl ester (commercially available as metvix) both in vitro and in vivo, and to check whether the liposome-entrapped precursors of photosensitizers can induce the expression of metalloproteinases (MMPs) in animal tumor cells and in other tissues from tumor-bearing rats and in selected cell lines in vitro. We also checked whether the application of tissue inhibitors of matrix metalloproteinases (TIMPs) has any effect on MMPs in the above-mentioned experimental models, and if they can cause complete inhibition of MMP expression. Immunohistochemical studies revealed that after the PDT, the intensity of expression of MMPs in healthy animals was very low and seen in single cells only. After the PDT in tumor-bearing rats, MMP-3 was expressed in the tumor cells with the highest intensity of staining in the tissues directly adjacent to the tumors, while MMP-2 and -9 were not found. In the control groups, there was no observed expression of MMPs. In vitro studies showed that MMP-3 was expressed in MCF-7 cells after PDT, but MMP-9 was not observed and MMP-2 was only seen in single cases. Our studies confirmed that the application of an MMP-3 inhibitor may block an induction of MMP-3 expression which had previously been initiated by PDT. The preliminary data obtained from cancer patients revealed that new precursors are effective in terms of PDT, and that using MMP inhibitors should be considered as a potential enhancing factor in clinical PDT.


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