Role of nitric oxide in the response to photooxidative stress in prostate cancer cells

D'Este, Francesca; Pietra, Emilia Della; Pazmay, Gretta Veronica Badillo; Xodo, Luigi E.; Rapozzi, Valentina

doi:10.1016/j.bcp.2020.114205

Cited by 10 publications

(10 citation statements)

References 144 publications

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“…While we demonstrated an anti-inflammatory effect (see the inhibition of TGF-β1 signaling and the physiological protective effect of NO in the cardiovascular system), NO has been demonstrated to play a crucial role in the development of chronic inflammation. As example, the presence of NO in cancer may regulate tumor-associated macrophage metabolism and function, favoring the persistence of inflammation in tumorigenesis and cancer stemness [ 63 , 64 , 65 , 66 , 67 ]. These findings appear tissue-specific, since in most of the reports the association high NO levels with inflammation, oxidative status, DNA damage and tumorigenesis has been described for cancer of the gastrointestinal apparatus, upper airways, the reproductive organs and the breast.…”

Section: Discussionmentioning

confidence: 99%

The Nitric Oxide Donor [Zn(PipNONO)Cl] Exhibits Antitumor Activity through Inhibition of Epithelial and Endothelial Mesenchymal Transitions

Ciccone

Filippelli

Bacchella

et al. 2022

Cancers

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Exogenous nitric oxide appears a promising therapeutic approach to control cancer progression. Previously, a nickel-based nonoate, [Ni(SalPipNONO)], inhibited lung cancer cells, along with impairment of angiogenesis. The Zn(II) containing derivatives [Zn(PipNONO)Cl] exhibited a protective effect on vascular endothelium. Here, we have evaluated the antitumor properties of [Zn(PipNONO)Cl] in human lung cancer (A549) and melanoma (A375) cells. Metastasis initiates with the epithelial–mesenchymal transition (EMT) process, consisting of the acquisition of invasive and migratory properties by tumor cells. At not cytotoxic levels, the nonoate significantly impaired A549 and A375 EMT induced by transforming growth factor-β1 (TGF-β1). Reduction of the mesenchymal marker vimentin, upregulated by TGF-β1, and restoration of the epithelial marker E-cadherin, reduced by TGF-β1, were detected in both tumor cell lines in the presence of Zn-nonoate. Further, the endothelial–mesenchymal transition achieved in a tumor-endothelial cell co-culture was assessed. Endothelial cells co-cultured with A549 or A375 acquired a mesenchymal phenotype with increased vimentin, alpha smooth muscle actin and Smad2/3, and reduced VE-cadherin. The presence of [Zn(PipNONO)Cl] maintained a typical endothelial phenotype. In conclusion, [Zn(PipNONO)Cl] appears a promising therapeutic tool to control tumor growth and metastasis, by acting on both tumor and endothelial cells, reprogramming the cells toward their physiologic phenotypes.

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Section: Discussionmentioning

confidence: 99%

The Nitric Oxide Donor [Zn(PipNONO)Cl] Exhibits Antitumor Activity through Inhibition of Epithelial and Endothelial Mesenchymal Transitions

Ciccone

Filippelli

Bacchella

et al. 2022

Cancers

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“…Accumulation of intracellular ROS may damage DNA, proteins and membranes of organelles, which ultimately activates apoptosis to exert anticancer activity (36,37). Therefore, induction of oxidative stress by anticancer drugs is an effective therapeutic strategy to kill cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…The overaccumulation of ROS and RNS creates oxidative and nitrosative stress and plays important roles in regulating cell survival and death (36,37). As shown in Figures 6A and S6, QTMP induced ROS generation in a concentration-dependent manner, as indicated by a rightward shift in fluorescence in the FACS plots in SW480, HCT116 and Caco2 cells.…”

Section: Qtmp-induced Apoptosis Depends On Ros and Rns In Crc Cellsmentioning

confidence: 92%

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QTMP, a Novel Thiourea Polymer, Causes DNA Damage to Exert Anticancer Activity and Overcome Multidrug Resistance in Colorectal Cancer Cells

et al. 2021

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Colorectal cancer (CRC) is one of the most common malignancies, and multidrug resistance (MDR) severely restricts the effectiveness of various anticancer drugs. Therefore, the development of novel anticancer drugs for the treatment of CRC patients with MDR is necessary. Quaternized thiourea main-chain polymer (QTMP) is a self-assembled nanoparticle with good water solubility. Notably, QTMP is not a P-glycoprotein (P-gp) substrate, and it exhibits potent cytotoxic activity against CRC cells, including HCT116/DDP and P-gp-mediated multidrug-resistant Caco2 cells. QTMP also exhibits a strong anticancer activity against SW480 cells in vivo. Interestingly, reactive oxygen species (ROS) and reactive nitrogen species (RNS) production were increased in a concentration-dependent manner in QTMP-treated HCT116, SW480 and Caco2 cells. Importantly, QTMP causes DNA damage in these CRC cells via direct insertion into the DNA or regulation of ROS and/or RNS production. QTMP also induces caspase-dependent apoptosis via overproduction of ROS and RNS. Therefore, QTMP is a promising anticancer therapeutic agent for patients with CRC, including those cancer cells with P-gp-mediated MDR. The present study also indicates that the design and synthesis of anticancer drugs based on thiourea polymers is promising and valuable, thereby offering a new strategy to address MDR, and provides reference resources for further investigations of thiourea polymers.

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“…In addition to the NFκB-YY1-RKIP connection, high and low NO levels can also modulate EMT and drug resistance in PC3 cells via NFκB-RKIP-GSK3β-NRF2, where high NO inhibits NFκB, leading to RKIP upregulation, GSK3β stabilization and NRF2 downregulation along with inhibition of EMT and sensitization to drug treatment. Low NO produces the opposite actions [ 140 ].…”

Section: Rkip As a Tumor Suppression Of Prostate Cancer (Pc)mentioning

confidence: 99%

Insights of RKIP-Derived Suppression of Prostate Cancer

Dong

Lin

Kapoor

et al. 2021

Cancers

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Prostate cancer (PC) is a major cause of cancer death in men. The disease has a great disparity in prognosis. Although low grade PCs with Gleason scores ≤ 6 are indolent, high-risk PCs are likely to relapse and metastasize. The standard of care for metastatic PC (mPC) remains androgen deprivation therapy (ADT). Resistance commonly occurs in the form of castration resistant PC (CRPC). Despite decades of research efforts, CRPC remains lethal. Understanding of mechanisms underpinning metastatic progression represents the overarching challenge in PC research. This progression is regulated by complex mechanisms, including those regulating PC cell proliferation, epithelial–mesenchymal transition (EMT), and androgen receptor (AR) signaling. Among this PC metastatic network lies an intriguing suppressor of PC metastasis: the Raf kinase inhibitory protein (RKIP). Clinically, the RKIP protein is downregulated in PC, and showed further reduction in mPC. In xenograft mouse models for PC, RKIP inhibits metastasis. In vitro, RKIP reduces PC cell invasion and sensitizes PC cells to therapeutic treatments. Mechanistically, RKIP suppresses Raf-MEK-ERK activation and EMT, and modulates extracellular matrix. In return, Snail, NFκB, and the polycomb protein EZH2 contribute to inhibition of RKIP expression. In this review, we will thoroughly analyze RKIP’s tumor suppression actions in PC.

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Role of nitric oxide in the response to photooxidative stress in prostate cancer cells

Cited by 10 publications

References 144 publications

The Nitric Oxide Donor [Zn(PipNONO)Cl] Exhibits Antitumor Activity through Inhibition of Epithelial and Endothelial Mesenchymal Transitions

The Nitric Oxide Donor [Zn(PipNONO)Cl] Exhibits Antitumor Activity through Inhibition of Epithelial and Endothelial Mesenchymal Transitions

QTMP, a Novel Thiourea Polymer, Causes DNA Damage to Exert Anticancer Activity and Overcome Multidrug Resistance in Colorectal Cancer Cells

Insights of RKIP-Derived Suppression of Prostate Cancer

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