Nitroxide-functional PEGylated nanostars arrest cellular oxidative stress and exhibit preferential accumulation in co-cultured breast cancer cells

2021 ◽  
Author(s):  
Nam V. Dao ◽  
Francesca Ercole ◽  
Yuhuan Li ◽  
Thomas P. Davis ◽  
Lisa M. Kaminskas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Preferential Accumulation ◽  
Biological Performance

Conjugation to nanostars enhances the biological performance of TEMPO.

Antitumor Action of Amygdalin on Human Breast Cancer Cells by Selective Sensitization to Oxidative Stress

2018 ◽  
Vol 71 (3) ◽  
pp. 483-490 ◽  
Author(s):  
Muayad Mehdi Abboud ◽  
Wajdy Al Awaida ◽  
Hakam Hasan Alkhateeb ◽  
Asia Numan Abu-Ayyad
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Antitumor Action ◽  
Human Breast Cancer Cells ◽  
Human Breast

Oxidative Stress in Caffeine Action on the Proliferation and Death of Human Breast Cancer Cells MCF-7 and MDA-MB-231

2020 ◽  
pp. 1-11
Author(s):  
Kaliana Larissa Machado ◽  
Poliana Camila Marinello ◽  
Thamara Nishida Xavier Silva ◽  
Cássio Fernando Nunes Silva ◽  
Rodrigo Cabral Luiz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Mcf 7

scholarly journals Poly-ADP-Ribosylation of Estrogen Receptor-Alpha by PARP1 Mediates Antiestrogen Resistance in Human Breast Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 43 ◽  
Author(s):  
Nicholas Pulliam ◽  
Jessica Tang ◽  
Weini Wang ◽  
Fang Fang ◽  
Riddhi Sood ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Target Genes ◽  
Tamoxifen Resistance ◽  
Tamoxifen Treatment ◽  
Dependent Manner ◽  
Tamoxifen Resistant

Therapeutic targeting of estrogen receptor-α (ERα) by the anti-estrogen tamoxifen is standard of care for premenopausal breast cancer patients and remains a key component of treatment strategies for postmenopausal patients. While tamoxifen significantly increases overall survival, tamoxifen resistance remains a major limitation despite continued expression of ERα in resistant tumors. Previous reports have described increased oxidative stress in tamoxifen resistant versus sensitive breast cancer and a role for PARP1 in mediating oxidative damage repair. We hypothesized that PARP1 activity mediated tamoxifen resistance in ERα-positive breast cancer and that combining the antiestrogen tamoxifen with a PARP1 inhibitor (PARPi) would sensitize tamoxifen resistant cells to tamoxifen therapy. In tamoxifen-resistant vs. -sensitive breast cancer cells, oxidative stress and PARP1 overexpression were increased. Furthermore, differential PARylation of ERα was observed in tamoxifen-resistant versus -sensitive cells, and ERα PARylation was increased by tamoxifen treatment. Loss of ERα PARylation following treatment with a PARP inhibitor (talazoparib) augmented tamoxifen sensitivity and decreased localization of both ERα and PARP1 to ERα-target genes. Co-administration of talazoparib plus tamoxifen increased DNA damage accumulation and decreased cell survival in a dose-dependent manner. The ability of PARPi to overcome tamoxifen resistance was dependent on ERα, as lack of ERα-mediated estrogen signaling expression and showed no response to tamoxifen-PARPi treatment. These results correlate ERα PARylation with tamoxifen resistance and indicate a novel mechanism-based approach to overcome tamoxifen resistance in ER+ breast cancer.

scholarly journals DJ-1 Proteoforms in Breast Cancer Cells: The Escape of Metabolic Epigenetic Misregulation

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1968
Author(s):  
Domenica Scumaci ◽  
Erika Olivo ◽  
Claudia Vincenza Fiumara ◽  
Marina La Chimia ◽  
Maria Teresa De Angelis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Glycolytic Flux ◽  
Proliferative Potential ◽  
Moderate Increase ◽  
Reactive Carbonyl Species ◽  
Proteomic Approach ◽  
Age Related

Enhanced glycolysis is a hallmark of breast cancer. In cancer cells, the high glycolytic flux induces carbonyl stress, a damaging condition in which the increase of reactive carbonyl species makes DNA, proteins, and lipids more susceptible to glycation. Together with glucose, methylglyoxal (MGO), a byproduct of glycolysis, is considered the main glycating agent. MGO is highly diffusible, enters the nucleus, and can react with easily accessible lysine- and arginine-rich tails of histones. Glycation adducts on histones undergo oxidization and further rearrange to form stable species known as advanced glycation end-products (AGEs). This modification alters nucleosomes stability and chromatin architecture deconstructing the histone code. Formation of AGEs has been associated with cancer, diabetes, and several age-related diseases. Recently, DJ-1, a cancer-associated protein that protects cells from oxidative stress, has been described as a deglycase enzyme. Although its role in cell survival results still controversial, in several human tumors, its expression, localization, oxidation, and phosphorylation were found altered. This work aimed to explore the molecular mechanism that triggers the peculiar cellular compartmentalization and the specific post-translational modifications (PTM) that, occurring in breast cancer cells, influences the DJ-1 dual role. Using a proteomic approach, we identified on DJ-1 a novel threonine phosphorylation (T125) that was found, by the in-silico tool scansite 4, as part of a putative Akt consensus. Notably, this threonine is in addition to histidine 126, a key residue involved in the formation of catalytic triade (glu18-Cys106-His126) inside the glioxalase active site of DJ. Interestingly, we found that pharmacological modulation of Akt pathway induces a functional tuning of DJ-1 proteoforms, as well as their shuttle from cytosol to nucleus, pointing out that pathway as critical in the development of DJ-1 pro-tumorigenic abilities. Deglycase activity of DJ-1 on histones proteins, investigated by coupling 2D tau gel with LC-MS/MS and 2D-TAU (Triton-Acid-Urea)-Western blot, was found correlated with its phosphorylation status that, in turn, depends from Akt activation. In normal conditions, DJ-1 acts as a redox-sensitive chaperone and as an oxidative stress sensor. In cancer cells, glycolytic rewiring, inducing increased reactive oxygen species (ROS) levels, enhances AGEs products. Alongside, the moderate increase of ROS enhances Akt signaling that induces DJ-1-phosphorylation. When phosphorylated DJ-1 increases its glyoxalase activity, the level of AGEs on histones decreases. Therefore, phospho-DJ-1 prevents glycation-induced histones misregulation and its Akt-related hyperactivity represents a way to preserve the epigenome landscape sustaining proliferation of cancer cells. Together, these results shed light on an interesting mechanism that cancer cells might execute to escape the metabolic induced epigenetic misregulation that otherwise could impair their malignant proliferative potential.

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