Photodynamic Oxidative Stress Targets Cancer as Well as Cancer Stem Cells

2022 ◽  
pp. 1-19
Author(s):  
Anine Crous ◽  
Sajan George ◽  
Heidi Abrahamse
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Cancer Stem Cells

Combination of Histone Deacetylase Inhibitor with Cu(II) 5,5- diethylbarbiturate Complex Induces Apoptosis in Breast Cancer Stem Cells: A Promising Novel Approach

2020 ◽  
Vol 21 ◽  
Author(s):  
Merve Erkisa ◽  
Nazlihan Aztopal ◽  
Elif Erturk ◽  
Engin Ulukaya ◽  
Veysel T. Yilmaz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Histone Deacetylases ◽  
Caspase 3 ◽  
Cancer Cell Line ◽  
Annexin V ◽  
Tumor Formation ◽  
Dependent Manner

Background: Cancer stem cells (CSC) are subpopulation within the tumor that acts a part in the initiation, progression, recurrence, resistance to drugs and metastasis of cancer. It is well known that epigenetic changes lead to tumor formation in cancer stem cells and show drug resistance. Epigenetic modulators and /or their combination with different agents have been used in cancer therapy. Objective: In our study we scope out the effects of combination of a histone deacetylases inhibitor, valproic acid (VPA), and Cu(II) complex [Cu(barb-κN)(barb-κ2N,O)(phen-κN,N’)]·H2O] on cytotoxicity/apoptosis in a stem-cell enriched population (MCF-7s) obtained from parental breast cancer cell line (MCF-7). Methods: Viability of the cells was measured by the ATP assay. Apoptosis was elucidated via the assessment of caspase-cleaved cytokeratin 18 (M30 ELISA) and a group of flow cytometry analysis (caspase 3/7 activity, phosphatidylserine translocation by annexin V-FITC assay, DNA damage and oxidative stress) and 2ˈ,7ˈ–dichlorofluorescein diacetate staining. Results: The VPA combined with Cu(II) complex showed anti proliferative activity on MCF-7s cells in a dose- and time-dependently. Treatment with combination of 2.5 mM VPA and 3.12 μM Cu(II) complex induces oxidative stress in a time-dependent manner, as well as apoptosis that is evidenced by the increase in caspase 3/7 activity, positive annexin-V-FITC, and increase in M30 levels. Conclusion: The results suggest that the combination therapy induces apoptosis following increased oxidative stress, thereby making it a possible promising therapeutic strategy that further analysis is required.

scholarly journals Oxidative stress induces senescence in breast cancer stem cells

2019 ◽  
Vol 514 (4) ◽  
pp. 1204-1209 ◽  
Author(s):  
Guangxian Zhong ◽  
Shenghui Qin ◽  
Danyelle Townsend ◽  
Bradley A. Schulte ◽  
Kenneth D. Tew ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Breast Cancer Stem Cells

scholarly journals Chronic Oxidative Stress Promotes Molecular Changes Associated with Epithelial Mesenchymal Transition, NRF2, and Breast Cancer Stem Cell Phenotype

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 633 ◽  
Author(s):  
Ana Čipak Gašparović ◽  
Lidija Milković ◽  
Nadia Dandachi ◽  
Stefanie Stanzer ◽  
Iskra Pezdirc ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Therapy Resistance ◽  
Mesenchymal Transition ◽  
Chronic Oxidative Stress ◽  
Emt Markers

Oxidative stress plays a role in carcinogenesis, but it also contributes to the modulation of tumor cells and microenvironment caused by chemotherapeutics. One of the consequences of oxidative stress is lipid peroxidation, which can, through reactive aldehydes such as 4-hydroxy-2-nonenal (HNE), affect cell signaling pathways. On the other hand, cancer stem cells (CSC) are now recognized as a major factor of malignancy by causing metastasis, relapse, and therapy resistance. Here, we evaluated whether oxidative stress and HNE modulation of the microenvironment can influence CSC growth, modifications of the epithelial to mesenchymal transition (EMT) markers, the antioxidant system, and the frequency of breast cancer stem cells (BCSC). Our results showed that oxidative changes in the microenvironment of BCSC and particularly chronic oxidative stress caused changes in the proliferation and growth of breast cancer cells. In addition, changes associated with EMT, increase in glutathione (GSH) and Nuclear factor erythroid 2-related factor 2 (NRF2) were observed in breast cancer cells grown on HNE pretreated collagen and under chronic oxidative stress. Our results suggest that chronic oxidative stress can be a bidirectional modulator of BCSC fate. Low levels of HNE can increase differentiation markers in BCSC, while higher levels increased GSH and NRF2 as well as certain EMT markers, thereby increasing therapy resistance.

Superparamagnetic Iron Oxide Nanoparticles Induce Ferroptosis of Human Ovarian Cancer Stem Cells by Weakening Cellular Autophagy

2020 ◽  
Vol 16 (11) ◽  
pp. 1612-1622
Author(s):  
Yongyi Huang ◽  
Jiajia Lin ◽  
Ying Xiong ◽  
Juan Chen ◽  
Xiling Du ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ovarian Cancer ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Superparamagnetic Iron Oxide ◽  
Oxide Nanoparticles ◽  
Human Ovarian Cancer ◽  
Ovarian Cancer Stem Cells

Human ovarian cancer stem cells (HuOCSCs) are the main source of ovarian cancer recurrence, metastasis, and drug resistance. Superparamagnetic iron oxide nanoparticles (SPIONs) are well-known nucleic acid or drug carriers owing to their controllable properties, superior stability, and easy modification. However, whether SPIONs can inhibit the activity of HuOCSCs by inducing ferroptosis remains unclear. In the present study, we isolated CD44+ /CD133+ HuOCSCs from tumours of four patients with clear cell ovarian cancer and added 0.2 mM SPIONs for mixed culture. Transmission electron microscopy showed that SPION-treated HuOCSCs contained multiple high-density electron clouds. Prussian blue staining showed high concentrations of iron ions in the cells. In vitro , SPIONs treatment of HuOCSCs inhibited cell proliferation, migration, and soft agar clone formation, weakened their resistance to multiple chemotherapeutics, and induced cell death. In vivo , SPIONs pretreatment of HuOCSCs significantly reduced their tumour-forming ability and induced angiogenesis in nude mice. Further, SPIONs induced the accumulation of reactive oxygen species in HuOCSCs and induced oxidative stress. qPCR analysis indicated that SPIONs-treated HuOCSCs had reduced expression of tumour stem cell markers (CD117, NANOG, CD133, and SOX2), cell proliferation factors (KI67, CCND), autophagy-related factors (ATG3, ATG5, MAP1ALC3a, MAP1ALC3b, and MAP1ALC3c), and certain negative regulators of ferroptosis, while the mRNA expression levels of cell death-related proteins (BAK1 and BID), and certain positive regulators of ferroptosis were significantly increased. Overall, our findings suggest that SPIONs induce oxidative stress and decrease autophagy activity in ovarian cancer stem cells, activate ferroptosis, and inhibit their proliferation, invasion, drug resistance, and tumorigenic ability.

scholarly journals Role of Oxidative Stress in Stem, Cancer, and Cancer Stem Cells

Cancers ◽  
2010 ◽  
Vol 2 (2) ◽  
pp. 859-884 ◽  
Author(s):  
Ahmed Abdal Dayem ◽  
Hye-Yeon Choi ◽  
Jung-Hyun Kim ◽  
Ssang-Goo Cho
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Cancer Stem Cells

scholarly journals Peroxiredoxin II Regulates Cancer Stem Cells and Stemness-Associated Properties of Cancers

Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 305 ◽  
Author(s):  
Nisansala Chandimali ◽  
Dong Jeong ◽  
Taeho Kwon
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Redox Status ◽  
Cell Phenotype ◽  
Therapeutic Effects ◽  
Cellular Functions ◽  
Unlimited Growth ◽  
Current Therapies

Cancer stem cells (CSCs) represent a sub-population of cancer cells with the ability to regulate stemness-associated properties which are specifically responsible for unlimited growth of cancers, generation of diverse cancer cells in differentiated state and resistance to existing chemotherapy and radiotherapy. Even though, current therapies destroy majority of cancer cells, it is believed to leave CSCs without eradicating which may be the conceptualization for chemoresistance and radio-resistance. Reactive oxygen species (ROS) maintain stem cells and regulate the stemness-associated properties of cancers. Beyond the maximum limit, ROS can damage cellular functions of cancers by subjecting them to oxidative stress. Thus, maintenance of ROS level plays an important role in cancers to regulate stemness-associated properties. Peroxiredoxin II (Prx II) is a member of peroxiredoxin antioxidant enzyme family which considers as a regulator of ROS in cellular environments by modulating redox status to maintain CSC phenotype and stemness properties. Prx II has cell type-dependent expression in various types of cancer cells and overexpression or silenced expression of Prx II in cancers is associated with stem cell phenotype and stemness-associated properties via activation or deactivation of various signaling pathways. In this review, we summarized available studies on Prx II expression in cancers and the mechanisms by which Prx II takes parts to regulate CSCs and stemness-associated properties. We further discussed the potential therapeutic effects of altering Prx II expression in cancers for better anticancer strategies by sensitizing cancer cells and stem cells to oxidative stress and inhibiting stemness-associated properties.

scholarly journals Phenethyl Isothiocyanate Exposure Promotes Oxidative Stress and Suppresses Sp1 Transcription Factor in Cancer Stem Cells

2019 ◽  
Vol 20 (5) ◽  
pp. 1027 ◽  
Author(s):  
Bijaya Upadhyaya ◽  
Yi Liu ◽  
Moul Dey
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Transcription Factor ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Therapy Resistance ◽  
Dependent Manner ◽  
Phenethyl Isothiocyanate ◽  
Concentration Dependent Manner

Aldehyde dehydrogenase 1 (ALDH1) is a cytosolic marker of cancer stem cells (CSCs), which are a sub-population within heterogeneous tumor cells. CSCs associate with therapy-resistance, self-renewal, malignancy, tumor-relapse, and reduced patient-survival window. ALDH1-mediated aldehyde scavenging helps CSCs to survive a higher level of oxidative stress than regular cancer cells. Cruciferous vegetable-derived phenethyl isothiocyanate (PEITC) selectively induces reactive oxygen species (ROS), leading to apoptosis of cancer cells, but not healthy cells. However, this pro-oxidant role of PEITC in CSCs is poorly understood and is investigated here. In a HeLa CSCs model (hCSCs), the sphere-culture and tumorsphere assay showed significantly enriched ALDHhi CSCs from HeLa parental cells (p < 0.05). Aldefluor assay and cell proliferation assay revealed that PEITC treatments resulted in a reduced number of ALDHhi hCSCs in a concentration-dependent manner (p < 0.05). In the ROS assay, PEITC promoted oxidative stress in hCSCs (p ≤ 0.001). Using immunoblotting and flow cytometry techniques, we reported that PEITC suppressed the cancer-associated transcription factor (Sp1) and a downstream multidrug resistance protein (P-glycoprotein) (both, p < 0.05). Furthermore, PEITC-treatment of hCSCs, prior to xenotransplantation in mice, lowered the in vivo tumor-initiating potential of hCSCs. In summary, PEITC treatment suppressed the proliferation of ALDH1 expressing cancer stem cells as well as key factors that are involved with drug-resistance, while promoting oxidative stress and apoptosis in hCSCs.

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