Photodynamic therapy combined to cisplatin potentiates cell death responses of cervical cancer cells

Abstract

BackgroundPhotodynamic therapy (PDT) has proven to be a promising alternative to current cancer treatments, especially if combined with conventional approaches. The technique is based on the administration of a non-toxic photosensitizing agent to the patient with subsequent localized exposure to a light source of a specific wavelength, resulting in a cytotoxic response to oxidative damage. The present study intended to evaluate in vitro the type of induced death and the genotoxic and mutagenic effects of PDT alone and associated with cisplatin.MethodsWe used the cell lines SiHa (ATCC® HTB35™), C-33 A (ATCC® HTB31™) and HaCaT cells, all available at Dr. Christiane Soares’ Lab. Photosensitizers were Photogem (PGPDT) and methylene blue (MBPDT), alone or combined with cisplatin. Cell death was accessed through Hoechst and Propidium iodide staining and caspase-3 activity. Genotoxicity and mutagenicity were accessed via flow cytometry with anti-gama-H2AX and micronuclei assay, respectively. Data were analyzed by one-way ANOVA with Tukey’s posthoc test.ResultsBoth MBPDT and PGPDT induced caspase-independent death, but MBPDT induced the morphology of typical necrosis, while PGPDT induced morphological alterations most similar to apoptosis. Cisplatin predominantly induced apoptosis, and the combined therapy induced variable rates of apoptosis- or necrosis-like phenotypes according to the cell line, but the percentage of dead cells was always higher than with monotherapies. MBPDT, either as monotherapy or in combination with cisplatin, was the unique therapy to induce significant damage to DNA (double strand breaks) in the three cell lines evaluated. However, there was no mutagenic potential observed for the damage induced by MBPDT, since the few cells that survived the treatment have lost their clonogenic capacity.ConclusionsOur results elicit the potential of combined therapy in diminishing the toxicity of antineoplastic drugs. Ultimately, photodynamic therapy mediated by either methylene blue or Photogem as monotherapy or in combination with cisplatin has low mutagenic potential, which supports its safe use in clinical practice for the treatment of cervical cancer.

In vitro combined effect of Doxorubicin and sulfonated zinc Phthalocyanine–mediated photodynamic therapy on MCF-7 breast cancer cells

“…The results indicate that combination of DOX and ZnPcS-PDT triggers apoptosis and leads to increased yield of apoptotic MCF-7 cells. A similar study by de Freitas et al 39 on cervical cancer cells noted an increased rate of apoptosis and percentage of dead cells with combined treatment of cisplatin and photogem-mediated PDT. Our results suggest that PDT can potentially serve as an adjuvant therapy for DOX.…”

DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance

“…PDT is based on the administration of a photosensitizing agent (PS), topic or systemically, to the patient with subsequent local exposure to a light source of a specific wavelength, leading to the formation of highly cytotoxic reactive oxygen species. Among its several advantages, worthy of note are the minimum systemic adverse effects due to its double selectivity (de Freitas et al, 2017). In the past decade, the DNA repair genes in astrocytoma 9 application of PDT to treat GBM has been investigated and proven to be a promising approach, both in vitro and in vivo (Chakrabarti et al, 2013;Akimoto, 2016).…”

The Rationale for “Laser-Induced Thermal Therapy (LITT) and Intratumoral Cisplatin” Approach for Cancer Treatment

“…However, the requirement for an oxygen environment is a major difficulty as many malignant, and most aggressive, cancer cells are hypoxic [ 68 ]. There are several in vitro studies that have demonstrated the synergistic effect of the combination of PDT with cisplatin in the treatment of various types of cancer cells, with better results obtained than for isolated approaches [ 69 , 70 , 71 , 72 , 73 , 74 , 75 ]. There have also been some clinical trials probing the efficacy of PDT with concomitant cisplatin [ 76 , 77 ].…”