Cytotoxic effect of nitric oxide on human hematological malignant cells.

Abstract

We investigated the cytotoxic effect of nitric oxide (NO) on primary culture of human hematological malignant cells. Sodium nitroprusside (SNP), an NO donor, had cytotoxic effects on the cells of some patients with malignant lymphoma (ML), acute myelocytic leukemia (AML) or chronic myelomonocytic leukemia (CMMoL), but not with multiple myeloma. Cultured cells from the ML patient remained sensitive to SNP after the cells became resistant to anti-cancer drugs. In contrast, the cells from the patients with AML and CMMoL became resistant to SNP while anti-cancer drugs remained effective. In samples of the cells of the patients with ML and AML, the number of CD3 positive lymphoma cell was decreased by SNP and the number of CD33 negative cells and normal B lymphocytes (CD19 positive cells) were increased. In the cells of the patient with ML, apoptosis was induced by SNP. SNP had no effect on lymphocytes of healthy volunteers. These results suggest that SNP had an anti-tumor effect on human hematological malignant cells.Nitric oxide (NO) is a multifunctional molecule produced in a variety of mammalian cells. At physiological levels, NO is associated with neurotransmission and vasodilatation. At higher levels, NO has tumoricidal and bacteriocidal effects [1,2]. In the cell-mediated immune responses, NO is produced in macrophages, neutrophils and lymphocytes [3][4][5]. Several lines of evidence indicate that NO has cytotoxic effects on human cell lines Vol. 49 No.

Dual effect of nitric oxide in immortalized and malignant human oral keratinocytes: induction of apoptosis and differentiation

“…The NO and NO‐related species have delineated antiproliferative, cytotoxic, and apoptotic effects of NO on several tumor cells, including leukemia, pancreatic, hepatic, and colon cancer (16–19). Although recently studies demonstrated NO‐induced apoptotic effects on oral cancer cells (20, 21), comparative effects of proliferation and differentiation on oral immortalized vs. malignant keratinocytes cells towards NO was not reported.…”

Winner of the society for biomaterials young investigator award for the annual meeting of the society for biomaterials, April 11–14, 2018, Atlanta, GA: S‐nitrosated poly(propylene sulfide) nanoparticles for enhanced nitric oxide delivery to lymphatic tissues

“…18 A therapeutic of particular interest for the treatment of lymphatic-related diseases is nitric oxide (NO), an extremely promiscuous signaling molecule that takes part in a variety of physiological processes ranging from vasodilation, [19][20][21][22][23] to neural signaling, 24 to immune cell cytotoxic defenses. [25][26][27][28] Because of the important role that NO plays in multiple physiological processes, there have been many attempts at modulating NO for therapeutic purposes. For example, NO delivered in the form of nitrate is used to control pain from angina, a disease affecting nine million people in the US with 500,000 new cases every year, and has been found to annually cost the healthcare system around $1.9 billion.…”

“…33 NO has also been explored for the treatment of various cancers, including lymphoma where a variety of NO donors have been shown to be chemosensitizers [34][35][36] as well as exhibit direct cytotoxicity. 25,[36][37][38][39] Despite the versatility of NO as a potential therapeutic in a broad array of pathologies, several challenges exist with utilizing NO for lymphatic-related therapy. First, NO participates in many interrelated physiological processes that each have different requirements for NO signaling.…”

“…A therapeutic of particular interest for the treatment of lymphatic‐related diseases is nitric oxide (NO), an extremely promiscuous signaling molecule that takes part in a variety of physiological processes ranging from vasodilation, to neural signaling, to immune cell cytotoxic defenses . Because of the important role that NO plays in multiple physiological processes, there have been many attempts at modulating NO for therapeutic purposes.…”

“…For pulmonary diseases NO is inhaled in its gaseous form, and is the current standard of care for persistent pulmonary hypertension in newborns, which affects 1.9 per 1000 live births . NO has also been explored for the treatment of various cancers, including lymphoma where a variety of NO donors have been shown to be chemosensitizers as well as exhibit direct cytotoxicity …”