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Article

Photodynamic Therapy with Zinc Phthalocyanine Inhibits the Stemness and Development of Colorectal Cancer: Time to Overcome the Challenging Barriers?

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Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51666-14731, Iran
2
Student Research Committee, Tabriz University of Medical Sciences, Tabriz 51666-14731, Iran
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Biophotonic Research Center, Islamic Azad University, Tabriz Branch, Tabriz 51579-44533, Iran
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Research Institute for Applied Physics and Astronomy, University of Tabriz, Tabriz 51666-16471, Iran
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Istituto Tumori BariGiovanni Paolo II, Istituto Nazionale dei Tumori (IRCCS), 70124 Bari, Italy
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Department of Biomedical Sciences and Human Oncology, School of Medicine, University of Bari Aldo Moro, 70124 Bari, Italy
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Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz 51666-14731, Iran
*
Authors to whom correspondence should be addressed.
Co-last author.
Academic Editors: Carlos J. P. Monteiro, Catarina I. V. Ramos and M. Amparo F. Faustino
Molecules 2021, 26(22), 6877; https://doi.org/10.3390/molecules26226877
Received: 26 July 2021 / Revised: 3 November 2021 / Accepted: 4 November 2021 / Published: 15 November 2021
(This article belongs to the Special Issue Photodynamic Therapy in Cancer Treatment 2021)
Photodynamic therapy (PDT) is a light-based cancer therapy approach that has shown promising results in treating various malignancies. Growing evidence indicates that cancer stem cells (CSCs) are implicated in tumor recurrence, metastasis, and cancer therapy resistance in colorectal cancer (CRC); thus, targeting these cells can ameliorate the prognosis of affected patients. Based on our bioinformatics results, SOX2 overexpression is significantly associated with inferior disease-specific survival and worsened the progression-free interval of CRC patients. Our results demonstrate that zinc phthalocyanine (ZnPc)-PDT with 12 J/cm2 or 24 J/cm2 irradiation can substantially decrease tumor migration via downregulating MMP9 and ROCK1 and inhibit the clonogenicity of SW480 cells via downregulating CD44 and SOX2. Despite inhibiting clonogenicity, ZnPc-PDT with 12 J/cm2 irradiation fails to downregulate CD44 expression in SW480 cells. Our results indicate that ZnPc-PDT with 12 J/cm2 or 24 J/cm2 irradiation can substantially reduce the cell viability of SW480 cells and stimulate autophagy in the tumoral cells. Moreover, our results show that ZnPc-PDT with 12 J/cm2 or 24 J/cm2 irradiation can substantially arrest the cell cycle at the sub-G1 level, stimulate the intrinsic apoptosis pathway via upregulating caspase-3 and caspase-9 and downregulating Bcl-2. Indeed, our bioinformatics results show considerable interactions between the studied CSC-related genes with the studied migration- and apoptosis-related genes. Collectively, the current study highlights the potential role of ZnPc-PDT in inhibiting stemness and CRC development, which can ameliorate the prognosis of CRC patients. View Full-Text
Keywords: photodynamic therapy; zinc phthalocyanine; cancer stem cell; colorectal cancer; stemness; prognosis; metastasis photodynamic therapy; zinc phthalocyanine; cancer stem cell; colorectal cancer; stemness; prognosis; metastasis
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MDPI and ACS Style

Gholizadeh, M.; Doustvandi, M.A.; Mohammadnejad, F.; Shadbad, M.A.; Tajalli, H.; Brunetti, O.; Argentiero, A.; Silvestris, N.; Baradaran, B. Photodynamic Therapy with Zinc Phthalocyanine Inhibits the Stemness and Development of Colorectal Cancer: Time to Overcome the Challenging Barriers? Molecules 2021, 26, 6877. https://doi.org/10.3390/molecules26226877

AMA Style

Gholizadeh M, Doustvandi MA, Mohammadnejad F, Shadbad MA, Tajalli H, Brunetti O, Argentiero A, Silvestris N, Baradaran B. Photodynamic Therapy with Zinc Phthalocyanine Inhibits the Stemness and Development of Colorectal Cancer: Time to Overcome the Challenging Barriers? Molecules. 2021; 26(22):6877. https://doi.org/10.3390/molecules26226877

Chicago/Turabian Style

Gholizadeh, Mahsa, Mohammad Amin Doustvandi, Fateme Mohammadnejad, Mahdi Abdoli Shadbad, Habib Tajalli, Oronzo Brunetti, Antonella Argentiero, Nicola Silvestris, and Behzad Baradaran. 2021. "Photodynamic Therapy with Zinc Phthalocyanine Inhibits the Stemness and Development of Colorectal Cancer: Time to Overcome the Challenging Barriers?" Molecules 26, no. 22: 6877. https://doi.org/10.3390/molecules26226877

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