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

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6877
Author(s):  
Mahsa Gholizadeh ◽  
Mohammad Amin Doustvandi ◽  
Fateme Mohammadnejad ◽  
Mahdi Abdoli Shadbad ◽  
Habib Tajalli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Photodynamic Therapy ◽  
Cancer Therapy ◽  
Therapy Resistance ◽  
Zinc Phthalocyanine ◽  
Apoptosis Pathway ◽  
Intrinsic Apoptosis Pathway ◽  
Sw480 Cells ◽  
Tumoral Cells

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.

scholarly journals A Novel Mechanism of the c-Myc/NEAT1 Axis Mediating Colorectal Cancer Cell Response to Photodynamic Therapy Treatment

2021 ◽  
Vol 11 ◽  
Author(s):  
Kuijie Liu ◽  
Sanlin Lei ◽  
Yong Kuang ◽  
Qianqian Jin ◽  
Dongju Long ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Photodynamic Therapy ◽  
Cell Viability ◽  
Critical Role ◽  
Tumor Model ◽  
P53 Signaling ◽  
Sw480 Cells ◽  
Therapy Treatment ◽  
Hct116 Cells

Photodynamic therapy (PDT) is considered a potential treatment regimen for colorectal cancer cases (CRC). p53 signaling and the miR-124/iASPP axis play an essential role in the PDT resistance of CRC cells. PDT treatment downregulated NEAT1 expression in p53wt HCT116 and RKO cells. In these two cell lines, NEAT1 silencing enhanced the suppressive effects of PDT on cell viability and apoptosis. Within the subcutaneously implanted tumor model, NEAT1 silencing enhanced PDT-induced suppression on tumor growth. Regarding p53-deleted HCT116 cells, PDT only moderately affected cell proliferation but induced downregulation of NEAT1. NEAT1 directly targeted miR-124, acting as a ceRNA, competing with iASPP for miR-124 binding, and counteracting miR-124–mediated repression on iASPP under PDT treatment. NEAT1 silencing was enhanced, whereas miR-124 inhibition attenuated PDT effects on CRC cells; miR-124 inhibition significantly reversed the roles of NEAT1 silencing in PDT-treated CRC cells. miR-124 negatively correlated with NEAT1 and iASPP, respectively, whereas NEAT1 and iASPP positively correlated with each other. PDT downregulated c-Myc in CRC cells, and c-Myc activated the transcription of NEAT1 through the targeting of its promoter region. Within p53mut SW480 cells, PDT failed to alter cell viability and apoptosis but still downregulated c-Myc, NEAT1, and iASPP and upregulated miR-124. In p53 mutant high-abundant CRC tissues, c-Myc and NEAT1 were up-regulated, and miR-124 was downregulated. In c-Myc high-abundant CRC tissues, NEAT1 and iASPP were up-regulated, and miR-124 was downregulated. The critical role of the c-Myc/NEAT1 axis in mediating CRC response to PDT treatment via the miR-124/iASPP/p53 feedback loop was conclusively demonstrated.

scholarly journals Cell Plasticity and Prostate Cancer: The Role of Epithelial–Mesenchymal Transition in Tumor Progression, Invasion, Metastasis and Cancer Therapy Resistance

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2795
Author(s):  
Sofia Papanikolaou ◽  
Aikaterini Vourda ◽  
Spyros Syggelos ◽  
Kostis Gyftopoulos
Keyword(s):  
Prostate Cancer ◽  
Cancer Therapy ◽  
Tumor Progression ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Tumor ◽  
Therapy Resistance ◽  
Cellular Process ◽  
Cell Plasticity ◽  
Mesenchymal Transition

Prostate cancer, the second most common malignancy in men, is characterized by high heterogeneity that poses several therapeutic challenges. Epithelial–mesenchymal transition (EMT) is a dynamic, reversible cellular process which is essential in normal embryonic morphogenesis and wound healing. However, the cellular changes that are induced by EMT suggest that it may also play a central role in tumor progression, invasion, metastasis, and resistance to current therapeutic options. These changes include enhanced motility and loss of cell–cell adhesion that form a more aggressive cellular phenotype. Moreover, the reverse process (MET) is a necessary element of the metastatic tumor process. It is highly probable that this cell plasticity reflects a hybrid state between epithelial and mesenchymal status. In this review, we describe the underlying key mechanisms of the EMT-induced phenotype modulation that contribute to prostate tumor aggressiveness and cancer therapy resistance, in an effort to provide a framework of this complex cellular process.

scholarly journals Impact of Quantum Dot Surface on Complex Formation with Chlorin e6 and Photodynamic Therapy

Nanomaterials ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 9 ◽  
Author(s):  
Artiom Skripka ◽  
Dominyka Dapkute ◽  
Jurga Valanciunaite ◽  
Vitalijus Karabanovas ◽  
Ricardas Rotomskis
Keyword(s):  
Photodynamic Therapy ◽  
Cancer Therapy ◽  
Complex Formation ◽  
Chemical Properties ◽  
Disease Diagnosis ◽  
Chlorin E6 ◽  
Deep Tissue ◽  
Physico Chemical

Nanomaterials have permeated various fields of scientific research, including that of biomedicine, as alternatives for disease diagnosis and therapy. Among different structures, quantum dots (QDs) have distinctive physico-chemical properties sought after in cancer research and eradication. Within the context of cancer therapy, QDs serve the role of transporters and energy donors to photodynamic therapy (PDT) drugs, extending the applicability and efficiency of classic PDT. In contrast to conventional PDT agents, QDs’ surface can be designed to promote cellular targeting and internalization, while their spectral properties enable better light harvesting and deep-tissue use. Here, we investigate the possibility of complex formation between different amphiphilic coating bearing QDs and photosensitizer chlorin e6 (Ce6). We show that complex formation dynamics are dependent on the type of coating—phospholipids or amphiphilic polymers—as well as on the surface charge of QDs. Förster’s resonant energy transfer occurred in every complex studied, confirming the possibility of indirect Ce6 excitation. Nonetheless, in vitro PDT activity was restricted only to negative charge bearing QD-Ce6 complexes, correlating with better accumulation in cancer cells. Overall, these findings help to better design such and similar complexes, as gained insights can be straightforwardly translated to other types of nanostructures—expanding the palette of possible therapeutic agents for cancer therapy.

scholarly journals The role of lineage plasticity in prostate cancer therapy resistance

2019 ◽  
pp. clincanres.1423.2019 ◽  
Author(s):  
Himisha Beltran ◽  
Andrew Hruszkewycz ◽  
Howard I. Scher ◽  
Jeffrey Hildesheim ◽  
Jennifer Isaacs ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Therapy ◽  
Therapy Resistance ◽  
Prostate Cancer Therapy

Role of SCFAs in gut microbiome and glycolysis for colorectal cancer therapy

2019 ◽  
Vol 234 (10) ◽  
pp. 17023-17049 ◽  
Author(s):  
Gang Wang ◽  
Yang Yu ◽  
Yu‐Zhu Wang ◽  
Jun‐Jie Wang ◽  
Rui Guan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Therapy ◽  
Gut Microbiome

scholarly journals Protein Expression Profiling Identifies Key Proteins and Pathways Involved in Growth Inhibitory Effects Exerted by Guggulsterone in Human Colorectal Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1478 ◽  
Author(s):  
Leo ◽  
Therachiyil ◽  
Siveen ◽  
Uddin ◽  
Kulinski ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
P53 Protein ◽  
Colorectal Cancer Cell Line ◽  
Proteomic Profiling ◽  
Human Colorectal Cancer ◽  
Altered Expression ◽  
Apoptosis Pathway ◽  
Intrinsic Apoptosis Pathway ◽  
Hct 116

Colorectal cancer (CRC) is a leading killer cancer worldwide and one of the most common malignancies with increasing incidences of mortality. Guggulsterone (GS) is a plant sterol used for treatment of various ailments such as obesity, hyperlipidemia, diabetes, and arthritis. In the current study, anti-cancer effects of GS in human colorectal cancer cell line HCT 116 was tested, potential targets identified using mass spectrometry-based label-free shotgun proteomics approach and key pathways validated by proteome profiler antibody arrays. Comprehensive proteomic profiling identified 14 proteins as significantly dysregulated. Proteins involved in cell proliferation/migration, tumorigenesis, cell growth, metabolism, and DNA replication were downregulated while the protein with functional role in exocytosis/tumor suppression was found to be upregulated. Our study evidenced that GS treatment altered expression of Bcl-2 mediated the mitochondrial release of cytochrome c which triggered the formation of apoptosome as well as activation of caspase-3/7 leading to death of HCT 116 cells via intrinsic apoptosis pathway. GS treatment also induced expression of p53 protein while p21 expression was unaltered with no cell cycle arrest. In addition, GS was found to inhibit NF-kB signaling in colon cancer cells by quelling the expression of its regulated gene products Bcl-2, cIAP-1, and survivin.

Role of toll-like receptor 3 in prostate cancer therapy-resistance

2019 ◽  
Vol 18 (8) ◽  
pp. e3124
Author(s):  
X.M. Muresan ◽  
S. Drapela ◽  
E. Slabakova ◽  
J. Remsik ◽  
R. Fedr ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Therapy ◽  
Therapy Resistance ◽  
Toll Like Receptor ◽  
Prostate Cancer Therapy

scholarly journals MiR-141 Activates Nrf2-Dependent Antioxidant Pathway via Down-Regulating the Expression of Keap1 Conferring the Resistance of Hepatocellular Carcinoma Cells to 5-Fluorouracil

2015 ◽  
Vol 35 (6) ◽  
pp. 2333-2348 ◽  
Author(s):  
Liang Shi ◽  
Lili Wu ◽  
Zhanguo Chen ◽  
Jianrong Yang ◽  
Xiaofei Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Therapy ◽  
Nuclear Translocation ◽  
Therapy Resistance ◽  
Parental Cell ◽  
Significant Inhibition ◽  
Carcinoma Cells ◽  
Pcr Analysis ◽  
Hepatocellular Carcinoma Cells

Background: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. A major cause for the failure of cancer therapy is the development of chemoresistance. Although progress has been made in the study of the mechanisms underlying cancer cells resistance, little is known about the role of microRNAs (miRNAs) in cancer therapy resistance. Methods and Results: Fifteen miRNAs, including 6 up-regulated miRNAs (> 2.0-fold) and 9 down-regulated miRNAs (< 0.5-fold) were differentially expressed in 5-fluorouracil-resistant and their parental cell-lines (HepG2, HepG2/5-FU) by miRNA microarrays. Microarray results were confirmed by validating quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Up-regulation of miR-141 expression resulted in a significant inhibition of 5-FU-mediated cytotoxicity and apoptosis in various hepatocellular carcinoma cells-lines. Mechanically, miR-141 promoted Kelch-like ECH-associated protein 1 (Keap1) mRNA degradation by directly targeting the Keap1 3'untranslated region (3'UTR). Treatment with miR-141 mimics in parental HepG2 cells, restored miR-141 expression and reduced Keap1 levels, thereby resulting in erythroid transcription factor NFE2-L2 (Nrf2) nuclear translocation, activation of Nrf2-dependent HO-1 gene transcription, and subsequent enhancement in 5-FU resistance. Conversely, restoring the expression of Keap1 partly recovered 5-FU sensitivity by counteracting miR-141-mediated 5-FU resistance. Conclusion: Our study showed that miR-141 plays a key role in 5-FU resistance by down-regulating Keap1 expression, thereby reactivating the Nrf2-dependent antioxidant pathway, which may serve as a potential target for overcoming 5-FU resistance in hepatocellular carcinoma cells.

A nanoporous photosensitizing hydrogel based on chitosan cross-linked by zinc phthalocyanine: an injectable and pH-stimuli responsive system for effective cancer therapy

RSC Advances ◽  
2016 ◽  
Vol 6 (94) ◽  
pp. 91445-91452 ◽  
Author(s):  
Ali Reza Karimi ◽  
Azam Khodadadi ◽  
Mahnaz Hadizadeh
Keyword(s):  
Photodynamic Therapy ◽  
Cancer Therapy ◽  
Therapeutic Efficacy ◽  
Zinc Phthalocyanine ◽  
Stimuli Responsive ◽  
Zinc Phthalocyanines ◽  
Tumor Selectivity ◽  
Biological Environment ◽  
Low Solubility ◽  
Effective Cancer Therapy

Although zinc phthalocyanines (ZnPcs) have promising applications in photodynamic therapy (PDT), their therapeutic efficacy suffer from their low solubility in the biological environment and their lack of tumor selectivity.

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