Abstract
Glioblastoma multiforme is considered to be one of the most aggressive types of tumors of the central nervous system, with a poor prognosis and short survival periods of ~ one year. The current protocol for glioblastoma treatment includes the surgical excision of the primary tumor followed by radio and chemotherapy. Photodynamic therapy (PDT) is considered a promising strategy for the treatment of several types of tumors. Phthalocyanines (Pcs) are good photosensitizers (PSs) for PDT because they induce cell death in several cellular models. ZnPc (Zn(II)phthalocyanine) is a well-known Pc, extensively tested in different cells and tumor models, but its evaluation on a glioblastoma model has been poorly studied. Herein, we compare the capacity of ZnPc and one of its derivatives, Zn(II)tetraminephthalocyanine (TAZnPc), to photoinactivate glioblastoma cells (T98G, MO59, LN229 and U87-MG) in culture. We measured the cellular uptake, the toxicity in the dark and the subcellular localization of the different Pcs, as well as the clonogenic capacity of surviving cells after PDT. The mechanism of cell death induced after PDT was determined by measuring caspase 3 activation, DNA fragmentation, phosphatidylserine externalization, mitochondrial morphological changes and loss of mitochondrial membrane potential as well as lysosomal membrane integrity. Overall, ZnPc and TAZnPc present good properties to be used as PSs with photoinactivation capacity on glioblastoma cells.
Highlights
At present, the protocol for treatment of Glioblastomas multiforme involves surgical resection followed by chemo and radiotherapy that results in an average survival time of approximately 14.6 months[5]
Cells were incubated during 18 hours with different concentrations of the Pc diluted in Dulbecco’s modified Eagle medium (DMEM) supplemented with 4% fetal bovine serum (FBS) and cell viability measured
Since it has been previously reported that Photodynamic therapy (PDT) treatment of tumor cells either in vitro or in vivo can induce cell death by different mechanisms[18], we evaluated the pathway of cell death triggered upon treatment of cells with the combination of Pc plus light
Summary
The protocol for treatment of Glioblastomas multiforme involves surgical resection followed by chemo and radiotherapy that results in an average survival time of approximately 14.6 months[5]. Singlet oxygen (1O2) and/or reactive oxygen species (ROS) that can damage cellular constituents leading to cell death[10,11] followed by tumor regression[12,13,14,15]. As these reactions occur only in the local area of the light-absorbing photosensitizer, the biological responses are limited to the area that has been irradiated. Phthalocyanines (Pcs) and their derivatives have been considered excellent PSs (second generation) for PDT in numerous types of tumors This type of molecule strongly absorbs in the red and near infrared regions of the visible spectrum, which corresponds to the tissue optical window[12,25,26]. To the best of our knowledge, only a few reports analyzed the effectiveness of Pcs on a glioblastoma cell model[30]
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