Photodynamic Therapy with Zinc Phthalocyanine Inhibits the Stemness and Development of Colorectal Cancer: Time to Overcome the Challenging Barriers?
Mahsa GholizadehMohammad Amin DoustvandiFateme MohammadnejadMahdi Abdoli ShadbadHabib TajalliOronzo BrunettiAntonella ArgentieroNicola SilvestrisBehzad BaradaranPublished in: Molecules (Basel, Switzerland) (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.
Keyphrases
- photodynamic therapy
- induced apoptosis
- cell cycle arrest
- endoplasmic reticulum stress
- cell death
- end stage renal disease
- cancer therapy
- signaling pathway
- cell cycle
- stem cells
- ejection fraction
- oxidative stress
- fluorescence imaging
- chronic kidney disease
- cancer stem cells
- newly diagnosed
- pi k akt
- drug delivery
- transcription factor
- prognostic factors
- epithelial mesenchymal transition
- risk assessment
- solid state