SILAC-based quantitative proteomics identified lysosome as a fast response target to PDT agent Gd-N induced oxidative stress in human ovarian cancer IGROV1 cells

2015 ◽  
Vol 11 (11) ◽  
pp. 3059-3067 ◽  
Author(s):  
Dandan Qi ◽  
Qianqian Wang ◽  
Hongguang Li ◽  
Tao Zhang ◽  
Rongfeng Lan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ovarian Cancer ◽  
Quantitative Proteomics ◽  
Fast Response ◽  
Human Ovarian Cancer ◽  
Proteomic Identification ◽  
Response Target

A PDT agent Gd-N was successfully applied in SILAC based quantitative proteomic identification of fast response targets to oxidative stress.

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 HSP60 Regulates Lipid Metabolism in Human Ovarian Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Na Li ◽  
Nannan Li ◽  
Siqi Wen ◽  
Biao Li ◽  
Yaying Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ovarian Cancer ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Pathway Network

Accumulating evidence demonstrates that cancer is an oxidative stress-related disease, and oxidative stress is closely linked with heat shock proteins (HSPs). Lipid oxidative stress is derived from lipid metabolism dysregulation that is closely associated with the development and progression of malignancies. This study sought to investigate regulatory roles of HSPs in fatty acid metabolism abnormality in ovarian cancer. Pathway network analysis of 5115 mitochondrial expressed proteins in ovarian cancer revealed various lipid metabolism pathway alterations, including fatty acid degradation, fatty acid metabolism, butanoate metabolism, and propanoate metabolism. HSP60 regulated the expressions of lipid metabolism proteins in these lipid metabolism pathways, including ADH5, ECHS1, EHHADH, HIBCH, SREBP1, ACC1, and ALDH2. Further, interfering HSP60 expression inhibited migration, proliferation, and cell cycle and induced apoptosis of ovarian cancer cells in vitro. In addition, mitochondrial phosphoproteomics and immunoprecipitation-western blot experiments identified and confirmed that phosphorylation occurred at residue Ser70 in protein HSP60, which might regulate protein folding of ALDH2 and ACADS in ovarian cancers. These findings clearly demonstrated that lipid metabolism abnormality occurred in oxidative stress-related ovarian cancer and that HSP60 and its phosphorylation might regulate this lipid metabolism abnormality in ovarian cancer. It opens a novel vision in the lipid metabolism reprogramming in human ovarian cancer.

Melatonin Sensitize the Ovarian Cancer Cells to Cisplatin through suppression of PI3K/Akt pathway

2021 ◽  
Author(s):  
Sahar Baghalsadriforoush ◽  
Morteza BAGHERI ◽  
isa abdirad ◽  
Fattah Sotoodehnejadnematalahi
Keyword(s):  
Oxidative Stress ◽  
Ovarian Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Akt Signaling ◽  
Ovarian Cancer Cells ◽  
Ros Generation ◽  
Human Ovarian Cancer ◽  
Akt Signaling Pathway

Abstract Background: The present study elucidated the effect of melatonin on oxidative stress status, the expression of pro-apoptotic protein (caspase 3 and cleaved caspase 3), anti-apoptotic proteins (X-linked apoptosis inhibitor protein (XIAP) and Survivin), and the activity of PI3K/Akt signaling pathway in human ovarian cancer cell line.Methods: Human ovarian cancer cells (OVCAR3) were treated with cisplatin, melatonin, cisplatin + melatonin, and siRNA Akt. Reactive oxygen species (ROS) levels were assessed using fluorimetric assay in the different groups. Moreover, protein expression of caspase-3, cleaved caspase 3, PI3K, Akt, phosphorylated (p)-Akt, XIAP, and Survivin were determined by Western blotting in all experimental groups.Results: Our results showed that administration of melatonin significantly increased intracellular ROS generation, the cleavage of caspase 3 and phosphorylation of Akt. This effect was more prominent in the combination therapy with cisplatin versus cisplatin alone. Akt siRNA transfection had similar effects on ROS generation, the cleavage of caspase 3, and phosphorylation of Akt. Interestingly, the levels of XIAP, PI3K, and Survivin were not significantly changed by any of these treatments.Conclusions: Taken together, this study suggests that combination therapy of cisplatin and melatonin increases apoptosis in the OVCAR-3 cells by inhibition of PI3K/Akt signaling pathway and exacerbation of oxidative stress.

scholarly journals DETECTION OF OXIDATIVE STRESS, APOPTOSIS AND MOLECULAR LESIONS IN HUMAN OVARIAN CANCER CELLS

2016 ◽  
Author(s):  
H. I. Falfushynska
Keyword(s):  
Oxidative Stress ◽  
Ovarian Cancer ◽  
Cancer Patients ◽  
Cathepsin D ◽  
Control Level ◽  
Protein Carbonyls ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Key Words Ovarian Cancer ◽  
Choline Esterase

<p>Background. Ovarian cancer has the highest mortality rate of gynaecological cancers. This is partly due to<br />the lack of effective screening markers. Indices of oxidative stress are well-recognized prognostic criteria for<br />tumorous transformation of tissue, but their value depends on the type of tumor and the stage of its development.<br />Objective. The aim of this study is to clarify the relationship between antioxidant/pro-oxidant ratio and the<br />signs of molecular lesions and apoptosis rate in blood of ovarian cancer patients and non-cancer ones.<br />Results. The ovarian cancer group is marked by antioxidant/prooxidant balance shifting to oxidative damage<br />in blood as the consequence of overexpression of oxyradicals (by 300%). Higher level of glutathione (by 366%),<br />lower level of metallothioneins (by 65%) as well as higher level of lipid peroxidation (by 174%) and protein carbonyls<br />(by 186%) in blood of ovarian cancer patients compared to the normal ovarian group have been observed. The<br />signs of cytotoxicity are determined in blood of ovarian cancer patients: an increased (compared to control) level<br />of DNA fragmentation (by 160%), choline esterase (up to twice), higher rate of both caspase dependent and<br />caspase independent lysosomal mediated apoptosis.<br />Conclusions. Cathepsin D activity both total and free, choline esterase activity, TBA-reactive substance and<br />protein carbonyls level in blood could be used as the predictive markers of worse prognosis and the signs of<br />human ovarian cancer.<br />KEY WORDS: ovarian cancer, oxidative stress, apoptosis, caspase-3, cathepsin D, choline esterase,<br />metallothionein.</p>

Proteomic Identification of Paclitaxel-Resistance Associated hnRNP A2 and GDI 2 Proteins in Human Ovarian Cancer Cells

2010 ◽  
Vol 9 (11) ◽  
pp. 5668-5676 ◽  
Author(s):  
Dong Hyeon Lee ◽  
Kwanghoe Chung ◽  
Ji-Ae Song ◽  
Tae-heon Kim ◽  
Haeyoun Kang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Paclitaxel Resistance ◽  
Proteomic Identification

scholarly journals Valspodar-modulated chemotherapy in human ovarian cancer cells SK-OV-3 and MDAH-2774

2019 ◽  
Author(s):  
Maciej Zalewski ◽  
Julita Kulbacka ◽  
Jolanta Saczko ◽  
Małgorzata Drag-Zalesinska ◽  
Anna Choromanska
Keyword(s):  
Oxidative Stress ◽  
Ovarian Cancer ◽  
Cell Death ◽  
Multidrug Resistance ◽  
Cell Viability ◽  
Cancer Cells ◽  
Gynecologic Oncology ◽  
Ovarian Cancer Cells ◽  
Control Group ◽  
Human Ovarian Cancer

Overcoming drug resistance in ovarian cancer is the overarching goal in gynecologic oncology. One way to increase drug cytotoxicity without increasing the drug dose is to simultaneously apply multidrug resistance modulator. Valspodar is the second generation P-glycoprotein 1 modulator capable of reversing multidrug resistance in different cancers. In this study, we evaluated the effect of valspodar and cisplatin co-treatment on cell viability, cell death and oxidative status in ovarian cancer cells. The two cisplatin-resistant human ovarian cancer cell lines SK-OV-3 and MDAH-2774 were treated with cisplatin, valspodar, or cisplatin+valspodar for 24 and 48 hours. Untreated cells were used as control group. Cell viability was evaluated by MTT assay. Cell death was assessed by TUNEL and comet assay. Lipid peroxidation (malondialdehyde) and protein thiol groups were analyzed as oxidative stress markers. The expression of mitochondrial superoxide dismutase (MnSOD) was assessed by immunocytochemistry. Valspodar effectively reduced the resistance of SK-OV-3 cells to cisplatin, as demonstrated by increased oxidative stress, decreased cell viability and increased apoptosis in SK-OV-3 cells co-treated with valspodar and cisplatin compared to other groups. However, valspodar did not affect the resistance of MDAH-2774 cells to cisplatin. Stronger staining for MnSOD in MDAH-2774 vs. SK-OV-3 cells after co-treatment with cisplatin and valspodar may determine the resistance of MDAH-2774 cell line to cisplatin.

Regulation of apoptosis in human ovarian cancer

1998 ◽  
Vol 5 (1) ◽  
pp. 46A-46A
Author(s):  
B TSANG ◽  
J LI ◽  
Q FENG ◽  
P LISTON ◽  
J KIM ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Human Ovarian Cancer
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