Imbalance between nitric oxide and superoxide anion induced by uncoupled nitric oxide synthase contributes to human metastatic melanoma development

Melo, Fabiana Henriques Machado de; Gonçalves, Diego Assis; Sousa, Ricardo Xisto de; Gonçalves, Jéssica; Silva, Douglas; Icimoto, Marcelo Yudi; Gimenez, Marcela; Angelis, Kátia De; Llesuy, Suzana; Fernandes, Denise de Castro; Laurindo, Francisco Rafael Martins; Jasiulionis, Miriam Galvonas

doi:10.1016/j.freeradbiomed.2018.10.149

Cited by 1 publication

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“…The transfection of iNOS in pancreatic cancer also allowed the tumor to escape the immune response [172]. NO has also been found to contribute to metastatic melanoma development [173] and human oral cancer [174]. The inhibition of iNOS has been identified as a therapeutic strategy to target these cancers.…”

Section: No Induction and No Donors In Cancer Therapymentioning

confidence: 99%

“…However, NO has also been shown to have various tumor-enhancing effects in triple-negative breast cancer [171], pancreatic cancer [172], melanoma [173], and oral cancer [174]. Although there have been several studies that have shown that iNOS can contribute to the growth of metastatic melanoma through modulating the tumor microenvironment [173], a recent study has shown that nonthermal plasma can induce immunogenic cell death of melanoma cancer cells [191]. This study was done in a vaccination assay in vivo using a dielectric barrier discharge system, which generated short-lived reactive oxygen species, including nitric oxide, and contributed to an anticancer response [191].…”

Section: Future Perspectives and Conclusionmentioning

confidence: 99%

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Nitric Oxide-Mediated Enhancement and Reversal of Resistance of Anticancer Therapies

Hays

Bonavida

2019

Antioxidants

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In the last decade, immune therapies against human cancers have emerged as a very effective therapeutic strategy in the treatment of various cancers, some of which are resistant to current therapies. Although the clinical responses achieved with many therapeutic strategies were significant in a subset of patients, another subset remained unresponsive initially, or became resistant to further therapies. Hence, there is a need to develop novel approaches to treat those unresponsive patients. Several investigations have been reported to explain the underlying mechanisms of immune resistance, including the anti-proliferative and anti-apoptotic pathways and, in addition, the increased expression of the transcription factor Yin-Yang 1 (YY1) and the programmed death ligand 1 (PD-L1). We have reported that YY1 leads to immune resistance through increasing HIF-1α accumulation and PD-L1 expression. These mechanisms inhibit the ability of the cytotoxic T-lymphocytes to mediate their cytotoxic functions via the inhibitory signal delivered by the PD-L1 on tumor cells to the PD-1 receptor on cytotoxic T-cells. Thus, means to override these resistance mechanisms are needed to sensitize the tumor cells to both cell killing and inhibition of tumor progression. Treatment with nitric oxide (NO) donors has been shown to sensitize many types of tumors to chemotherapy, immunotherapy, and radiotherapy. Treatment of cancer cell lines with NO donors has resulted in the inhibition of cancer cell activities via, in part, the inhibition of YY1 and PD-L1. The NO-mediated inhibition of YY1 was the result of both the inhibition of the upstream NF-κB pathway as well as the S-nitrosylation of YY1, leading to both the downregulation of YY1 expression as well as the inhibition of YY1-DNA binding activity, respectively. Also, treatment with NO donors induced the inhibition of YY1 and resulted in the inhibition of PD-L1 expression. Based on the above findings, we propose that treatment of tumor cells with the combination of NO donors, at optimal noncytotoxic doses, and anti-tumor cytotoxic effector cells or other conventional therapies will result in a synergistic anticancer activity and tumor regression.

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Section: No Induction and No Donors In Cancer Therapymentioning

confidence: 99%