Resistance of Lung Cancer Cells Grown as Multicellular Tumour Spheroids to Zinc Sulfophthalocyanine Photosensitization

Manoto, Sello Lebohang; Houreld, Nicolette Nadene; Abrahamse, Heidi

doi:10.3390/ijms160510185

Cited by 22 publications

(22 citation statements)

References 25 publications

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“…This mode of PDT which is indicated for multicellular tumours has been explored previously in vitro. The efficacy of PDT concerning a monolayer as compared to multicellular spheroids indicated that spheroids are more resistant to PDT, however this can be overcome using a dose dependent manner of inducing cell death [68]. Although PDT has successfully been used to treat lung cancer a major pitfall still include low tumour selectivity, especially in a scenario where the lung cancer's genomics are predisposed to malignant metastatic tumours [42].…”

Section: Resultsmentioning

confidence: 99%

Targeted Photodynamic Therapy for Improved Lung Cancer Treatment

Crous¹,

Abrahamse²

2018

Lung Cancer - Strategies for Diagnosis and Treatment

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Cancer develops from the outgrowth of a clonal population of cells with a genetic pathology to evade cell death and exponential proliferation. It has become a global burden with increasing mortality rates. Lung cancer is a major contributor to cancer fatalities. Conventional therapies have shown advances in treating lung cancer, but the successful eradication of cancer lies in targeting both cancer and cancer stem cells. Cancer stem cells (CSCs) are a ration of cells found within the tumour bulk, capable of cancer initiation, therapy resistance, metastasis and cancer relapse. Photodynamic therapy (PDT) has proven effective in treating lung cancer. PDT exerts selective cell death mechanisms toward cancerous cells. With the use of a photosensitizer (PS) which becomes excited upon irradiation with laser light at a specific wavelength, the PS forms reactive oxygen species (ROS) in turn killing neoplastic cells. Leading therapeutic sequel can be obtained by transcending PDT though combination therapies such as immunotherapy and nanotechnology which will enable PDT to target lung CSCs preventing lung cancer recurrence.

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Section: Resultsmentioning

confidence: 99%

Targeted Photodynamic Therapy for Improved Lung Cancer Treatment

Crous¹,

Abrahamse²

2018

Lung Cancer - Strategies for Diagnosis and Treatment

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“…31,32 ZnPcS-PDT also displays therapeutic efficacy in a similar manner within other cancer cell lines like human lungs (A549) and colon cancer cell (DLD-1). 33,34 The combination of DOX and ZnPcS-PDT was found to significantly decrease the viability and increase the cytotoxicity of cancer cells compared to the ZnPcS-PDT and DOX alone. CI analysis used to quantitatively evaluate the interactive effects of DOX and ZnPcS-PDT and combination showed a CI <1.…”

Section: Discussionmentioning

confidence: 99%

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

2017

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Doxorubicin is a broad-spectrum antibiotic and anticancer drug used to treat a variety of human malignancies like breast cancer and leukaemia. Unfortunately, a dose-dependent side effect of this drug is common, representing a major obstacle to its use despite its therapeutic efficacy. Photodynamic therapy is an emerging non-invasive potential adjuvant for conventional cancer treatment. In an attempt to circumvent the dose-limiting effect of doxorubicin, this study aimed to investigate cellular anticancer activity of doxorubicin and sulfonated zinc phthalocyanine-mediated photodynamic therapy on MCF-7 cells alone and in combination. Furthermore, we investigated the cell death pathway resulting from the combination treatment. MCF-7 cells were incubated with 0.5 µM concentration of doxorubicin for 20 h, afterwards, various concentrations of sulfonated zinc phthalocyanine were added and incubated for 4 h. Cells were irradiated using a 681.5 nm diode laser at 4.53 mW/cm for 18 min 24 s (5 J/cm). Cell viability and proliferation were measured using trypan blue assay and homogeneous adenosine triphosphate quantitation assay, respectively, while qualitative changes in cellular morphology were observed under inverted light microscopy. Cellular DNA damage was assessed under fluorescent microscopy and Annexin V/propidium iodide stain was used to investigate the cell death pathway. Findings from this study shown that combined treatment with doxorubicin and photodynamic therapy was more effective in inhibiting the proliferation and growth of MCF-7 cells. Overall, the results indicate that combination of smaller dose of doxorubicin with photodynamic therapy is a promising combined treatment strategy for breast carcinoma. However, this combination warrants further investigation.

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“…74 This is consistent with other MCS models that have demonstrated increased resistance of the 3D MCS model to pulmonary therapeutics relative to classic monoculture systems. 73,75 Recently, changes in migration, proliferation, and matrix remodeling have been observed using alveolar epithelial cells on microspheres encapsulated with a fibroblast hydrogel for a model of cancer progression and stromal-epithelial tumor microenvironment. 76 Spheroids have been utilized in a high-throughput 3D lung tumor assay to screen the effects of compounds on cellular proliferation and migration for small molecule therapeutic development; however, limited use of MCS models beyond drug discovery has been seen.…”

Section: Faber and Mcculloughmentioning

confidence: 99%

Through the Looking Glass: In Vitro Models for Inhalation Toxicology and Interindividual Variability in the Airway

Faber

McCullough

2018

Applied In Vitro Toxicology

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With 7 million deaths reported annually from air pollution alone, it is evident that adverse effects of inhaled toxicant exposures remain a major public health concern in the 21st century. Assessment and characterization of the impacts of air pollutants on human health stems from epidemiological and clinical studies, which have linked both outdoor and indoor air contaminant exposure to adverse pulmonary and cardiovascular health outcomes. Studies in animal models support epidemiological findings and have been critical in identifying systemic effects of environmental chemicals on cognitive abilities, liver disease, and metabolic dysfunction following inhalation exposure. Likewise, traditional monoculture systems have aided in identifying biomarkers of susceptibility to inhaled toxicants and served as a screening platform for safety assessment of pulmonary toxicants. Despite their contributions, in vivo and classic in vitro models have not been able to accurately represent the heterogeneity of the human population and account for interindividual variability in response to inhaled toxicants and susceptibility to the adverse health effects. Development of new technologies that can investigate genetic predisposition, are cost and time efficient, and are ethically sound, will enhance elucidation of mechanisms of inhalation toxicity, and aid in the development of novel pharmaceuticals and/or safety evaluation. This review will describe the classic and novel cell-based inhalation toxicity models and how these emerging technologies can be incorporated into regulatory or nonregulatory testing to address interindividual variability and improve overall human health.

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Resistance of Lung Cancer Cells Grown as Multicellular Tumour Spheroids to Zinc Sulfophthalocyanine Photosensitization

Cited by 22 publications

References 25 publications

Targeted Photodynamic Therapy for Improved Lung Cancer Treatment

Targeted Photodynamic Therapy for Improved Lung Cancer Treatment

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

Through the Looking Glass: In Vitro Models for Inhalation Toxicology and Interindividual Variability in the Airway

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