Amino Acid Profiling of Zinc Resistant Prostate Cancer Cell Lines: Associations With Cancer Progression

Kratochvílová, Monika; Raudenská, Martina; Heger, Zbyněk; Richtera, Lukáš; Cernei, Natalia; Adam, Vojtěch; Babula, Petr; Novàkovâ, Marie; Masařík, Michal; Gumulec, Jaromír

doi:10.1002/pros.23304

Cited by 19 publications

(15 citation statements)

References 49 publications

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“…Based on the evidence that in prostate cancer the amount of Zn is reduced, it was postulated that re-establishing normal intracellular Zn 2+ concentrations in prostatic tumours might restore a benign phenotype in malignant prostate cells. However, in contrast Kratochvilova et al and Holubova et al have convincingly showed that exogenous Zn 2+ drives tumour cells towards a more aggressive and resistant phenotype [ 53 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

Zinc ion dyshomeostasis increases resistance of prostate cancer cells to oxidative stress via upregulation of HIF1α

et al. 2018

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Zinc ions (Zn2+) are known to influence cell survival and proliferation. However the homeostatic regulation of Zn2+ and their role in prostate cancer (PC) progression is poorly understood. Therefore the subcellular distribution and uptake of Zn2+ in PC cells were investigated. Inductively coupled plasma mass spectroscopy and fluorescent microscopy with the Zn2+-specific fluorescent probe FluoZin-3 were used to quantify total and free Zn2+, respectively, in the normal prostate epithelial cell line (PNT1A) and three human PC cell lines (PC3, DU145 and LNCaP). The effects of Zn2+ treatment on proliferation and survival were measured in vitro using MTT assays and in vivo using mouse xenografts. The ability of Zn2+ to protect against oxidative stress via a HIF1α-dependent mechanism was investigated using a HIF1α knock-down PC3 model. Our results demonstrate that the total Zn2+ concentration in normal PNT1A and PC cells is similar, but PC3 cells contain significantly higher free Zn2+ than PNT1A cells (p < 0.01). PNT1A cells can survive better in the presence of high concentrations of Zn2+ than PC3 cells. Exposure to 10 µM Zn2+ over 72 hours significantly reduces PC3 cell proliferation in vitro but not in vivo. Zn2+ increases PC3 cell survival up to 2.3-fold under oxidative stress, and this protective effect is not seen in PNT1A cells or in a HIF1α-KD PC3 cell model. A state of Zn2+ dyshomeostasis exists in PC. HIF1α is an integral component of a Zn2+-dependent protective mechanism present in PC3 cells. This pathway may be clinically significant through its contribution to castrate-resistant PC survival.

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Section: Discussionmentioning

confidence: 99%

Zinc ion dyshomeostasis increases resistance of prostate cancer cells to oxidative stress via upregulation of HIF1α

et al. 2018

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“…This effect of cisplatin was also less pronounced in the presence of WR1065. Interestingly, in prostate cancer cell lines, zinc supplementation was found to increase cancer resilience to chemotherapy (Kratochvilova et al 2017 ).…”

Section: Resultsmentioning

confidence: 99%

Neuroprotective Role of Selected Antioxidant Agents in Preventing Cisplatin-Induced Damage of Human Neurons In Vitro

et al. 2019

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Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of platinum-based chemotherapy and decreases the quality of life of cancer patients. We compared neuroprotective properties of several agents using an in vitro model of terminally differentiated human cells NT2-N derived from cell line NT2/D1. Sodium azide and an active metabolite of amifostine (WR1065) increase cell viability in simultaneous treatment with cisplatin. In addition, WR1065 protects the non-dividing neurons by decreasing cisplatin caused oxidative stress and apoptosis. Accumulation of Pt in cisplatin-treated cells was heterogeneous, but the frequency and concentration of Pt in cells were lowered in the presence of WR1065 as shown by X-ray fluorescence microscopy (XFM). Transition metals accumulation accompanied Pt increase in cells; this effect was equally diminished in the presence of WR1065. To analyze possible chemical modulation of Pt-DNA bonds, we examined the platinum L III near edge spectrum by X-ray absorption spectroscopy. The spectrum found in cisplatin-DNA samples is altered differently by the addition of either WR1065 or sodium azide. Importantly, a similar change in Pt edge spectra was noted in cells treated with cisplatin and WR1065. Therefore, amifostine should be reconsidered as a candidate for treatments that reduce or prevent CIPN. Electronic supplementary material The online version of this article (10.1007/s10571-019-00667-7) contains supplementary material, which is available to authorized users.

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“…As known, amino acids often provide energy to support the proliferation of cancer cells and elevate levels of amino acids and their products are pathogenic factors for oxidative stress, neurological disorders and cancers. The tumor cells universally displayed high accumulation of amino acid 28 . Galactose metabolism together with fructose and mannose metabolism, from amino sugar and nucleotide sugar metabolism, also have relationship with ovarian cancer survival.…”

Section: Discussionmentioning

confidence: 99%

Proteomics analysis to reveal biological pathways and predictive proteins in the survival of high-grade serous ovarian cancer

Xie

Wang

Sun

et al. 2017

Sci Rep

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High-grade serous ovarian cancer (HGSC) is an aggressive cancer with a worse clinical outcome. Therefore, studies about the prognosis of HGSC may provide therapeutic avenues to improve patient outcomes. Since genome alteration are manifested at the protein level, we integrated protein and mRNA data of ovarian cancer from The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) and utilized the sparse overlapping group lasso (SOGL) method, a new mechanism-driven variable selection method, to select dysregulated pathways and crucial proteins related to the survival of HGSC. We found that biosynthesis of amino acids was the main biological pathway with the best predictive performance (AUC = 0.900). A panel of three proteins, namely EIF2B1, PRPS1L1 and MAPK13 were selected as potential predictive proteins and the risk score consisting of these three proteins has predictive performance for overall survival (OS) and progression free survival (PFS), with AUC of 0.976 and 0.932, respectively. Our study provides additional information for further mechanism and therapeutic avenues to improve patient outcomes in clinical practice.

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Amino Acid Profiling of Zinc Resistant Prostate Cancer Cell Lines: Associations With Cancer Progression

Cited by 19 publications

References 49 publications

Zinc ion dyshomeostasis increases resistance of prostate cancer cells to oxidative stress via upregulation of HIF1α

Zinc ion dyshomeostasis increases resistance of prostate cancer cells to oxidative stress via upregulation of HIF1α

Neuroprotective Role of Selected Antioxidant Agents in Preventing Cisplatin-Induced Damage of Human Neurons In Vitro

Proteomics analysis to reveal biological pathways and predictive proteins in the survival of high-grade serous ovarian cancer

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