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

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); th...

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Autores principales:	Mahsa Gholizadeh, Mohammad Amin Doustvandi, Fateme Mohammadnejad, Mahdi Abdoli Shadbad, Habib Tajalli, Oronzo Brunetti, Antonella Argentiero, Nicola Silvestris, Behzad Baradaran
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	photodynamic therapy zinc phthalocyanine cancer stem cell colorectal cancer stemness prognosis Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/3acb585402f24d3795f36e1d4e601510
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spelling	oai:doaj.org-article:3acb585402f24d3795f36e1d4e6015102021-11-25T18:28:03ZPhotodynamic Therapy with Zinc Phthalocyanine Inhibits the Stemness and Development of Colorectal Cancer: Time to Overcome the Challenging Barriers?10.3390/molecules262268771420-3049https://doaj.org/article/3acb585402f24d3795f36e1d4e6015102021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6877https://doaj.org/toc/1420-3049Photodynamic 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/cm<sup>2</sup> or 24 J/cm<sup>2</sup> 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/cm<sup>2</sup> irradiation fails to downregulate CD44 expression in SW480 cells. Our results indicate that ZnPc-PDT with 12 J/cm<sup>2</sup> or 24 J/cm<sup>2</sup> 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/cm<sup>2</sup> or 24 J/cm<sup>2</sup> 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.Mahsa GholizadehMohammad Amin DoustvandiFateme MohammadnejadMahdi Abdoli ShadbadHabib TajalliOronzo BrunettiAntonella ArgentieroNicola SilvestrisBehzad BaradaranMDPI AGarticlephotodynamic therapyzinc phthalocyaninecancer stem cellcolorectal cancerstemnessprognosisOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6877, p 6877 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	photodynamic therapy zinc phthalocyanine cancer stem cell colorectal cancer stemness prognosis Organic chemistry QD241-441
spellingShingle	photodynamic therapy zinc phthalocyanine cancer stem cell colorectal cancer stemness prognosis Organic chemistry QD241-441 Mahsa Gholizadeh Mohammad Amin Doustvandi Fateme Mohammadnejad Mahdi Abdoli Shadbad Habib Tajalli Oronzo Brunetti Antonella Argentiero Nicola Silvestris Behzad Baradaran Photodynamic Therapy with Zinc Phthalocyanine Inhibits the Stemness and Development of Colorectal Cancer: Time to Overcome the Challenging Barriers?
description	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/cm<sup>2</sup> or 24 J/cm<sup>2</sup> 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/cm<sup>2</sup> irradiation fails to downregulate CD44 expression in SW480 cells. Our results indicate that ZnPc-PDT with 12 J/cm<sup>2</sup> or 24 J/cm<sup>2</sup> 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/cm<sup>2</sup> or 24 J/cm<sup>2</sup> 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.
format	article
author	Mahsa Gholizadeh Mohammad Amin Doustvandi Fateme Mohammadnejad Mahdi Abdoli Shadbad Habib Tajalli Oronzo Brunetti Antonella Argentiero Nicola Silvestris Behzad Baradaran
author_facet	Mahsa Gholizadeh Mohammad Amin Doustvandi Fateme Mohammadnejad Mahdi Abdoli Shadbad Habib Tajalli Oronzo Brunetti Antonella Argentiero Nicola Silvestris Behzad Baradaran
author_sort	Mahsa Gholizadeh
title	Photodynamic Therapy with Zinc Phthalocyanine Inhibits the Stemness and Development of Colorectal Cancer: Time to Overcome the Challenging Barriers?
title_short	Photodynamic Therapy with Zinc Phthalocyanine Inhibits the Stemness and Development of Colorectal Cancer: Time to Overcome the Challenging Barriers?
title_full	Photodynamic Therapy with Zinc Phthalocyanine Inhibits the Stemness and Development of Colorectal Cancer: Time to Overcome the Challenging Barriers?
title_fullStr	Photodynamic Therapy with Zinc Phthalocyanine Inhibits the Stemness and Development of Colorectal Cancer: Time to Overcome the Challenging Barriers?
title_full_unstemmed	Photodynamic Therapy with Zinc Phthalocyanine Inhibits the Stemness and Development of Colorectal Cancer: Time to Overcome the Challenging Barriers?
title_sort	photodynamic therapy with zinc phthalocyanine inhibits the stemness and development of colorectal cancer: time to overcome the challenging barriers?
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/3acb585402f24d3795f36e1d4e601510
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Photodynamic Therapy with Zinc Phthalocyanine Inhibits the Stemness and Development of Colorectal Cancer: Time to Overcome the Challenging Barriers?

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