Myeloperoxidase and free iron levels: Potential biomarkers for early detection and prognosis of ovarian cancer

Fletcher, N.M.; Jiang, Zhongliang; Ali-Fehmi, Rouba; Levin, Nancy K.; Belotte, J; Tainsky, Michael A.; Diamond, Michael P.; Abu-Soûd, Husam M.; Saed, Ghassan M.

doi:10.3233/cbm-2012-0255

Cited by 31 publications

(30 citation statements)

References 41 publications

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“…Patients with colorectal tumors were found to have a higher number of MPO-positive cells in normal mucosa than did controls [48, 49]. Ovarian cancer tissue was found to have higher MPO levels than benign growths or inflammatory tissue [23]. Serum MPO levels were also found to be higher in stage II-IV ovarian cancer cases [23].…”

Section: Discussionmentioning

confidence: 99%

“…Ovarian cancer tissue was found to have higher MPO levels than benign growths or inflammatory tissue [23]. Serum MPO levels were also found to be higher in stage II-IV ovarian cancer cases [23]. Consistent with the association of higher levels of MPO with cancer risk, the higher expressing MPO G allele has been linked to increased risk for a number of cancers including lung [24, 31, 50, 51], breast [28, 52], ovarian [22], bladder [53], larynx [29], as well as myeloid leukemia [26].…”

Section: Discussionmentioning

confidence: 99%

“…This atypical expression can lead to oxidative damage to normal tissues contributing to atherosclerosis [13, 17, 18], Alzheimer’s disease [16, 19], and some types of cancer [20]. Earlier studies have also found evidence implicating MPO in the initiation or progression of ovarian cancer [21–23]. …”

Section: Introductionmentioning

confidence: 99%

“…Other studies have found higher levels of MPO in gynaecological or ovarian cancer tissue [21, 23, 38] as well as evidence that MPO promotes nitrosylation of caspase-3, potentially inhibiting apoptosis and enhancing survival of ovarian cancer cells [21]. …”

Section: Introductionmentioning

confidence: 99%

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Association of myeloperoxidase with ovarian cancer

et al. 2013

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Myeloperoxidase (MPO) is an oxidant generating enzyme normally restricted to myeloid cells, however aberrant MPO expression has been found to occur in non-myeloid cells in some disease states. The functional -463GA promoter polymorphism alters MPO expression levels. The -463G is within an SP1 binding site and is associated with higher gene expression. The G allele is most frequent with ~62% of European populations being GG homozygotes. The GA polymorphism has been associated with risk or survival in a variety of cancers including lung and breast cancer. In this study we determined the frequency of the -463G/A polymorphism in 230 ovarian cancer patients, 75 patients with borderline ovarian tumors, and 299 healthy controls. The GG genotype was found to be overrepresented in patients with early stage ovarian cancer (83.3% GG, p = 0.008) as compared to healthy controls (62% GG), suggesting MPO oxidants may increase risk. Immunohistochemical analysis revealed MPO expression in a subset of columnar ovarian epithelial carcinoma cells in early stage carcinomas.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of myeloperoxidase with ovarian cancer

et al. 2013

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“…12,13 Previous studies have demonstrated that alterations in redox signaling pathways are involved in the pathophysiology of EOC. 5,6,14,15 Reportedly, increasing iNOS activity can lead to S-nitrosylation of caspase-3 and decreased apoptosis in EOC cells. 5 Moreover, many have evidence outlining the role of glutathione and GS-XlMRPP2 efflux pumps as one of the mechanisms of cisplatin resistance.…”

Section: Introductionmentioning

confidence: 99%

The Role of Oxidative Stress in the Development of Cisplatin Resistance in Epithelial Ovarian Cancer

et al. 2014

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Objective: To investigate the role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer (EOC). Methods: Two parent EOC cell lines (MDAH-2774 and SKOV-3) and their chemoresistant counterparts (cisplatin, 50 mmol/L) were used. Total RNA was extracted and subjected to real-time reverse transcriptase polymerase chain reaction to evaluate the expression of glutathione reductase (GSR) and inducible nitric oxide synthase (iNOS), as well as nitrate/nitrite levels. Analysis of variance was used for main effects and Tukey for post hoc analysis at P < .05 for statistical significance. Results: Both cisplatin resistant cell lines displayed a significant decrease in GSR messenger RNA (mRNA) levels and activity (P < .01). As compared to sensitive controls, nitrate/nitrite levels were significantly higher in SKOV-3 cisplatin resistant cells while iNOS mRNA levels were significantly higher in MDAH-2774 cisplatin resistant cells (P < .05). Conclusion: Our data suggest that the development of cisplatin resistance tilts the balance toward a pro-oxidant state in EOC.

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Engineering Alendronate‐Composed Iron Nanochelator for Efficient Peritoneal Carcinomatosis Treatment

et al. 2022

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Iron is an essential element for various cellular metabolism. Cancer cells also have high requirement of iron in their proliferation, invasion, and metastasis processes. Alendronate (ALN), a kind of FDA-approved bisphosphonates with metal-chelating capability, is initially certified to selectively bind to intracellular Fe 3+ theoretically and experimentally in this study. Hence, CaALN iron nanochelator is rationally designed to kill cancer cells by synergism of Fe-depletion and calcium accumulation. In vitro experiments and RNA sequencing analysis indicate that CaALN nanomedicine inhibits the proliferation of cancer cells by depleting Fe, interfering with DNA replication, and triggering intracellular reactive oxygen species (ROS). Meanwhile, released Ca 2+ and ROS mutually promote and induce damage of cellular macromolecules, which leads to mitochondrial apoptosis of cancer cells. In an intraperitoneal disseminated mouse model with the human ovarian cancer cells SKOV3, CaALN nanoparticles selectively accumulate in tumor tissues and result in significant retardation of tumor growth and ascites formation. The mean survival time of SKOV3-bearing mice in treatment group is prolonged from 33 to 90 d. These results indicate that the alendronate-originated iron chelator can serve as an efficient strategy for the treatment of peritoneal carcinomatosis.

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Myeloperoxidase and free iron levels: Potential biomarkers for early detection and prognosis of ovarian cancer

Abstract: Collectively, these findings clearly indicate a role for the combination of serum MPO and free iron as biomarkers for early detection and prognosis of ovarian cancer.

Cited by 31 publications

References 41 publications

Association of myeloperoxidase with ovarian cancer

Association of myeloperoxidase with ovarian cancer

The Role of Oxidative Stress in the Development of Cisplatin Resistance in Epithelial Ovarian Cancer

Engineering Alendronate‐Composed Iron Nanochelator for Efficient Peritoneal Carcinomatosis Treatment

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