Nitric oxide inhibits topoisomerase II activity and induces resistance to topoisomerase II-poisons in human tumor cells

Kumar, Ashutosh; Ehrenshaft, Marilyn; Tokar, Erik J.; Mason, Ronald P.; Sinha, Birandra K.

doi:10.1016/j.bbagen.2016.04.009

Cited by 21 publications

(25 citation statements)

References 62 publications

(67 reference statements)

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“…This is in contrast to our studies with PPNO, an NO-donor, which had no effect on doxorubicin cytotoxicity against human breast MCF-7 and colon HT-29 cell lines in vitro [48]. We also found that * NO did not modulate the toxicity of doxorubicin against human melanoma cells [49].…”

Section: Nitric Oxide In Combination With Antitumor Agentscontrasting

confidence: 55%

Nitric Oxide: Friend or Foe in Cancer Chemotherapy and Drug Resistance: A Perspective

Sinha

2016

J Cancer Sci Ther

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A successful treatment of cancers in the clinic has been difficult to achieve because of the emergence of drug resistant tumor cells. While various approaches have been tried to overcome multi-drug resistance, it has remained a major road block in achieving complete success in the clinic. Extensive research has identified various mechanisms, including overexpression of P-glycoprotein 170, modifications in activating or detoxification enzymes (phase I and II enzymes), and mutation and/or decreases in target enzymes in cancer cells. However, nitric oxide and/or nitric oxide-related species have not been considered an important player in cancer treatment and or drug resistance. Here, we examine the significance of nitric oxide in the treatment and resistance mechanisms of various anticancer drugs. Furthermore, we describe the significance of recently reported effects of nitric oxide on topoisomerases and the development of resistance to topoisomerase-poisons in tumor cells.Nitric oxide is also implicated in cancer cell killing, cancer progression and metastasis and poor survival [13][14][15][16][17]. A poor clinical outcome is believed to result from * NO-induced rapid tumor growth, resulting in hypoxia, nutrient deprivation, poor drug delivery, and selection for drug-resistant tumor cells. In vivo, * NO is formed from L-arginine by nitric oxide synthase (NOS). Three forms of NOS have been identified, including neuronal (nNOS), endothelial (eNOS), and a Ca 2+ -independent inducible isoform (iNOS). High expression of iNOS and increased production of • NO have been described in many human tumors, including breast, prostate and colorectal cancers [17][18][19][20]. Increased and continuous generation of * NO plays a significant role in the regulation of cancer cell progression and carcinogenesis. Hibbs et al. [21,22] and Stuehr and Nathan [23] have shown that co-culturing of leukemia L1210 cells with activated peritoneal macrophages results in the inhibition of L1210 cell proliferation which is correlated with nitrite formation. Inhibitors of NOS (L-NAME) and myoglobin, a scavenger of * NO 2 were effective in inhibiting cell killing actions of the activated macrophages, suggesting that * NO is responsible for the killing actions of activated macrophages towards cancer cells.It is believed that DNA damage and apoptosis induced by * NO in tumor cells cause tumor cell death; studies are needed to explore processes to deliver the highest concentrations of * NO in tumor cells using NO-donors as single chemotherapeutic agents or in combination with other chemotherapeutic agents. While significant progress has been made in the last decade, the role of * NO/ * NO-related species remains poorly understood in chemotherapy and drug resistance. Here, we review the role of * NO/ * NO-related species in cancer chemotherapy

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Section: Nitric Oxide In Combination With Antitumor Agentscontrasting

confidence: 55%

Nitric Oxide: Friend or Foe in Cancer Chemotherapy and Drug Resistance: A Perspective

Sinha

2016

J Cancer Sci Ther

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“…La topoisomerasa alfa II (topoisomerase II alpha, TOP2A) que hace parte de una clase importante de enzimas nucleares responsables del mantenimiento de la topología del ADN y están involucradas en la reparación, la transcripción, la replicación y segregación de los cromosomas 35 y por último la alfa actina 4 (Alphaactinin-4 ACTN4) es una proteína de unión a actina que participa en la organización del citoesqueleto, esta reside tanto en el citoplasma como en el núcleo y se asocia físicamente con varios factores de transcripción 36 . La elevación de estas proteínas se presenta en las células con fase S del ciclo celular aberrantes, fase en la cual se evidencia la acción de las proteínas oncogénicas E6 y E7 del VPH [20][21][22] .…”

Section: Métodos Bioquímicos Para La Detección Y Prevención Del Vphunclassified

“…Es una técnica que utiliza una fase liquida que permite la hibridación por complementariedad del ADN viral con el ARN sintético de 13 genotipos de VPH-AR (16,18,31,33,35,39,45, 51, 52, 56, 58, 59 y 68) y cinco VPH-BR (6,11,42, 43 y 44). La hibridación es captada por anticuerpos fijados en los pozos de la microplaca, se elimina el exceso de reactivos, se agrega un revelador luminiscente y la emisión de luz es proporcional a la cantidad de ADN, otorgando una medida semicuantitativa de la carga viral 25 .…”

Section: Métodos De Biología Molecular Para La Detección Y Prevenciónunclassified

“…Tiene la capacidad de detectar 12 genotipos de VPH-AR (31,33,35,39,45, 51, 52, 56, 58, 59, 66 y 68) además de una identificación específica de los genotipos 16 y 18 con la ayuda de unos cebadores específicos para la β-globina. Se realiza por medio de una PCR en tiempo real con una amplificación detectada por fluorocromos, uno para las secuencias de los 12 VPH-AR y otros diferentes para 16, 18 y β-globina 16,29 .…”

Section: Métodos De Biología Molecular Para La Detección Y Prevenciónunclassified

“…Aptima HPV assay: aprobada por la FDA en el 2012 24 , manufacturado por Hologic Gen-Probe®, identifica 14 VPH-AR mediante una PCR en tiempo real (16,18,31,33,35,39,45, 51, 52, 56, 58, 59, 66 y 68) en tres procesos: Primero una identificación de la secuencia de trabajo. Segundo, una amplificación mediada por transcripción utilizando la enzima RNA polimerasa, las cuales permitirán una mayor cantidad de copias de ARN, posteriormente la enzima RNA transcriptasa reversa realiza un cambio de ARN a ADNc (ADN complementario).…”

Section: Métodos De Biología Molecular Para La Detección Y Prevenciónunclassified

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Modernas metodologías diagnosticas para la detección del Virus del Papiloma Humano y prevención del cáncer de cuello uterino

Rincón-Orozco

2017

revsal

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RESUMENLos Virus del Papiloma Humano (VPH) presentes en mucosa clasificados como de "alto riesgo" son agentes etiológicos de patologías oncológicas como cáncer de cuello uterino, ano, pene, vulva y cáncer orofaríngeo. Actualmente el principal método de tamizaje utilizado en Colombia para detección de cáncer de cuello uterino es la citología cervical, presentando una moderada cobertura en la población femenina y una sensibilidad cercana al 50%. El objetivo de este trabajo es describir las técnicas modernas utilizadas para la detección del VPH y prevención de los cánceres producidos por estos virus. Se llevó a cabo una revisión de literatura de las ultimas metodologías diagnosticas en la infección viral por VPH y marcadores de malignidad en muestras cervicales. La citología cervical es un recurso altamente específico y de bajo costo, pero poco sensible para la detección y prevención de cáncer de cuello uterino, que puede ser complementado con las tecnologías modernas revisadas con el objetivo de obtener un diagnóstico temprano del VPH como agente etiológico de estas enfermedades malignas.Palabras clave: Virus del Papilloma Humano, diagnóstico molecular, transformación maligna, infección crónica. ABSTRACTHuman Papilloma Viruses (HPVs) types present in mucosa and classified as "high risk" are etiologic agents of several oncological diseases as cervical cancer, anus, penis, vulva, and oropharyngeal cancer. Currently the principal method of screening used in Colombia for detecting cervical cancer is cervical cytology, which presents a moderate coverage in the population and sensitivity close to 50%. The objetive of this work is to describe new techniques for detection of Human Papillomavirus and cancer prevention for these viruses. We carried out a literature review of the cutting edge diagnostic methods for HPV viral infection. Cervical cytology is a highly specific resource, low-cost but low sensitivity for preventing cervical cancer, which can be supplemented with the modern technologies checked in order to obtain an early diagnosis of HPV as an etiologic agent of those malignancies.

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Nitric Oxide and Nitric Oxide Donors in Preclinical Studies of Breast and Prostate Cancer

Garrido

Walsh

Glynn

2017

Nitric Oxide as a Chemosensitizing Agent

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Nitric oxide inhibits topoisomerase II activity and induces resistance to topoisomerase II-poisons in human tumor cells

Cited by 21 publications

References 62 publications

Nitric Oxide: Friend or Foe in Cancer Chemotherapy and Drug Resistance: A Perspective

Nitric Oxide: Friend or Foe in Cancer Chemotherapy and Drug Resistance: A Perspective

Modernas metodologías diagnosticas para la detección del Virus del Papiloma Humano y prevención del cáncer de cuello uterino

Nitric Oxide and Nitric Oxide Donors in Preclinical Studies of Breast and Prostate Cancer

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