Tumor Size-Dependent Anticancer Efficacy of Chlorin Derivatives for Photodynamic Therapy

Photodynamic therapy (PDT) with a suitable photosensitizer molecule is a promising anticancer treatment. We evaluated two chlorin molecules as potential photosensitizers, methyl pyropheophorbide a (MPPa) and -methoxyl purpurinimide (NMPi), against A549 human lung adenocarcinoma cells in vitro as wel...

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Published in:International journal of molecular sciences 2018-05, Vol.19 (6), p.1596
Main Authors: Chang, Ji-Eun, Liu, Yang, Lee, Tae Heon, Lee, Woo Kyoung, Yoon, Il, Kim, Kwhanmien
Format: Article
Language:English
Subjects:
Adenocarcinoma
Cancer
cancer treatment
chlorin
Flow cytometry
Fluorescence
Light irradiation
Lung cancer
Photodynamic therapy
photodynamic therapy (PDT)
photosensitizer
Phototoxicity
Radiation
tumor size
Tumors
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Summary:Photodynamic therapy (PDT) with a suitable photosensitizer molecule is a promising anticancer treatment. We evaluated two chlorin molecules as potential photosensitizers, methyl pyropheophorbide a (MPPa) and -methoxyl purpurinimide (NMPi), against A549 human lung adenocarcinoma cells in vitro as well as in A549 tumor-bearing mice in vivo. Cell viability, microscopy, and fluorescence-activated cell sorting (FACS) analyses were performed for the in vitro studies. MPPa and NMPi showed high phototoxicity in vitro, which was dependent on the concentration of the photosensitizers as well as the light irradiation time. In the animal study, tumor volume change, tumor surface alterations, and hematoxylin & eosin (H&E) and terminal deoxyribonucleotidyl transferse-mediated dUTP nick-end labelling (TUNEL) staining analyses were performed and compared between small (tumor volume of 50 mm³) size of initial tumors. MPPa and NMPi showed high anticancer efficacy against small-size tumors, indicating that early treatment with PDT is effective. Especially, repeated two times PDT with NMPi allowed almost complete eradication against small-size tumors. However, MPPa and NMPi were not effective against large-size tumors. In conclusion, the two chlorin derivatives, MPPa and NMPi, show good anticancer efficacy as promising photosensitizers for PDT in vitro and in vivo. Moreover, their activity in vivo was significantly dependent on the initial tumor size in mice, which confirms the importance of early cancer treatment.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms19061596