Chemopreventive properties and mechanisms ofN-acetylcysteine. The experimental background

Flora, Silvio De; Cesarone, C. F.; Balansky, Roumen; Albini, Adriana; D’Agostini, Francesco; Bennicelli, Carlo; Bagnasco, Maria; Camoirano, Anna; Scatolini, L; Rovida, Alessandra

doi:10.1002/jcb.240590806

Cited by 115 publications

(59 citation statements)

References 22 publications

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“…4A). Antioxidants vitamin C and N-acetylcysteine can effectively scavenge a wide array of ROS and free radicals (52)(53)(54). The next set of experiments assessed their abilities to ameliorate UVB irradiationmediated ROS and PAF-R agonistic activity.…”

Section: Uvb Irradiation-mediated Production Of Ros and Paf-r Agonistmentioning

confidence: 99%

Platelet-activating Factor Receptor Agonists Mediate Xeroderma Pigmentosum A Photosensitivity

Yao

Harrison

Al-Hassani

et al. 2012

Journal of Biological Chemistry

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Background: Deficiency of the nucleotide excision repair protein xeroderma pigmentosum type A (XPA) is characterized by photosensitivity. Results: XPA-deficient cells and mice generate increased platelet-activating factor (PAF), oxidized glycerophosphocholines, and skin inflammation following ultraviolet B radiation with the skin inflammation blocked by PAF antagonists. Conclusion: PAF-R signaling mediates photosensitivity seen in XPA deficiency. Significance: These studies provide important insights into the mechanisms of photosensitivity.

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Section: Uvb Irradiation-mediated Production Of Ros and Paf-r Agonistmentioning

confidence: 99%

Platelet-activating Factor Receptor Agonists Mediate Xeroderma Pigmentosum A Photosensitivity

Yao

Harrison

Al-Hassani

et al. 2012

Journal of Biological Chemistry

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“…The protective effects of NAC in carcinogenesis have been shown to depend largely on the antigenotoxic activity associated with its nucleophilicity and antioxidant properties (2,3). NAC inhibits spontaneous mutagenicity as well as that induced by a number of chemical compounds or complex mixtures.…”

Section: Introductionmentioning

confidence: 99%

The Role of the Thiol N-Acetylcysteine in the Prevention of Tumor Invasion and Angiogenesis

Morini¹,

Cai²,

Aluigi³

et al. 1999

Int J Biol Markers

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We have extensively studied the effects of N-acetylcysteine (NAC), a cytoprotective drug that can prevent in vivo carcinogenesis. Here we review our findings NAC completely inhibits gelatinolytic activity of metalloproteases and chemotactic and invasive activities of tumor cells. In addition, NAC reduces the number of lung metastases when malignant murine melanoma cells are injected into nude mice. NAC treatment decreases the weight of primary tumors and produces a dose-related increase in tumor latency. Moreover, oral administration of NAC reduces the formation of spontaneous metastases. In experimental metastasis assays, we have found a synergistic reduction in the number of lung metastases after treatment with doxorubicin (DOX) and NAC in nude mice. In tumorigenicity and spontaneous metastasis assays, the combined administration of DOX and oral NAC again has shown synergistic effects on the frequency and weight of primary tumors and local recurrences and completely prevented the formation of lung metastases. The addition of NAC to endothelial cells strongly reduces their invasive activity in response to angiogenic stimuli. NAC inhibited the degradation and release of radiolabeled type IV collagen by activated endothelial cells, indicating that NAC blocks gelatinase activity. Oral administration of NAC reduces the angiogenic response induced by KS tumor cell products, confirming the ability of NAC to inhibit the invasive activity of endothelial cells in vivo and thereby blocking angiogenesis.

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“…The marked decrease of tumors observed in animals treated with NAC most likely reflects the detoxification of direct-acting mutagens due to its nucleophilic and anti-oxidant properties and less by interfering with the promotion stage of the carcinogenicity process. NAC has appeared to be one of the most promising cancer chemopreventive agents due to its beneficial effects in preclinical studies (15); however, when tested in a 2-year clinical trial (project Euroscan) (56), it was found ineffective on lung and neck cancer.…”

Section: Discussionmentioning

confidence: 99%

“…NAC (Sigma Chemical Co, St. Louis, MO) was administered by oral gavage at a dose of 125 mg/kg reported to be effective in mice (1,14,15). The maximum feasible dose for NAC was 125 mg/kg/day in mice.…”

Section: Methodsmentioning

confidence: 99%

“…These lesions included lung adenomas, bladder carcinoma, skin papilloma, colon carcinoma, and mammary adenocarcinoma. Oral administration of NAC (0.025-4 g/kg) revealed anticarcinogenic activity and a doserelated delay in formation of primary tumors (14,15). Among several anticarcinogenic mechanisms proposed were scavenging of reactive oxygen species (ROS), modulations of DNA repair and metabolism, regulation of cell cycle and apoptosis, and inhibition of invasions and metastasis (16).…”

Section: Introductionmentioning

confidence: 99%

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Slowing Tumorigenic Progression in TRAMP Mice and Prostatic Carcinoma Cell Lines Using Natural Anti-Oxidant from Spinach, NAO—A Comparative Study of Three Anti-Oxidants

et al. 2003

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The TRAMP model and human prostatic cancer (PCA) cell lines DU145 and PC3 are useful for chemopreventive studies. We compared the efficacy of 3 anti-oxidants [a water-soluble natural anti-oxidant, NAO (200 mg/kg), found in spinach leaves; epigallocatechin-3 gallate, EGCG (200 mg/kg), a major green tea polyphenol; and N -acetylcysteine, NAC (125 mg/kg)] plus vehicle in slowing spontaneous tumorigenic progression in TRAMP and wild-type male mice. Sacrifices occurred on weeks 5, 9, and 13. Prostatic histopathology and oxidative-stress blood markers were evaluated. Hyperplasias were ranked by a combination of severity grade and distribution (focal, multifocal, and diffuse). The effectivity of each tested compound in reducing the severity/focalness of hyperplasia varied from lobe to lobe. NAO exerted a significant effect on the dorsal and lateral lobes; NAC, on the anterior and ventral lobes, and EGCG, on the ventral lobe. When the most severe hyperplasia in all 4 lobes of TRAMPs was evaluated, only NAO reduced hyperplasia at weeks 9 and 13. Plasma peroxide levels in TRAMPs were reduced following oral administration of NAO or NAC for 13 weeks; EGCG only slightly reduced these levels. In NAO-treated DU145 and PC3 PCA cells, inhibition of cellular proliferation occurred in a dose-dependent manner, increasing numbers of G1 cells and reducing ROS levels. The anti-oxidative and antiproliferative properties of NAO may explain its efficacy in slowing the spontaneous prostatic carcinogenic process in the TRAMP and its effects in the cell lines.

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Chemopreventive properties and mechanisms ofN-acetylcysteine. The experimental background

Cited by 115 publications

References 22 publications

Platelet-activating Factor Receptor Agonists Mediate Xeroderma Pigmentosum A Photosensitivity

Platelet-activating Factor Receptor Agonists Mediate Xeroderma Pigmentosum A Photosensitivity

The Role of the Thiol N-Acetylcysteine in the Prevention of Tumor Invasion and Angiogenesis

Slowing Tumorigenic Progression in TRAMP Mice and Prostatic Carcinoma Cell Lines Using Natural Anti-Oxidant from Spinach, NAO—A Comparative Study of Three Anti-Oxidants

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