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Mutat Res. 2017 Oct;774:46-56. doi: 10.1016/j.mrrev.2017.09.001. Epub 2017 Sep 6.

Carcinogenic potential of sanguinarine, a phytochemical used in 'therapeutic' black salve and mouthwash.

Author information

1
Southern Cross Plant Science, Southern Cross University, Lismore, NSW, Australia; Wesley Medical Research Institute, Wesley Hospital, Auchenflower, QLD, Australia; Quality Use of Medicines Network, Queensland, Australia.
2
Southern Cross Plant Science, Southern Cross University, Lismore, NSW, Australia.
3
School of Medicine, University of Queensland, St Lucia, QLD, Australia.
4
Quality Use of Medicines Network, Queensland, Australia; School of Pharmacy and Pharmacology, Griffith University, Gold Coast Campus, Gold Coast, QLD, Australia.
5
Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palack√Ĺ University, Olomouc, Czech Republic.
6
Southern Cross Plant Science, Southern Cross University, Lismore, NSW, Australia. Electronic address: ben.liu@scu.edu.au.

Abstract

Black salves are escharotic skin cancer therapies in clinical use since the mid 19th century. Sanguinaria canadensis, a major ingredient of black salve formulations, contains a number of bioactive phytochemicals including the alkaloid sanguinarine. Despite its prolonged history of clinical use, conflicting experimental results have prevented the carcinogenic potential of sanguinarine from being definitively determined. Sanguinarine has a molecular structure similar to known polyaromatic hydrocarbon carcinogens and is a DNA intercalator. Sanguinarine also generates oxidative and endoplasmic reticulum stress resulting in the unfolded protein response and the formation of 8-hydroxyguanine genetic lesions. Sanguinarine has been the subject of contradictory in vitro and in vivo genotoxicity and murine carcinogenesis test results that have delayed its carcinogenic classification. Despite this, epidemiological studies have linked mouthwash that contains sanguinarine with the development of oral leukoplakia. Sanguinarine is also proposed as an aetiological agent in gallbladder carcinoma. This literature review investigates the carcinogenic potential of sanguinarine. Reasons for contradictory genotoxicity and carcinogenesis results are explored, knowledge gaps identified and a strategy for determining the carcinogenic potential of sanguinarine especialy relating to black salve are discussed. As patients continue to apply black salve, especially to skin regions suffering from field cancerization and skin malignancies, an understanding of the genotoxic and carcinogenic potential of sanguinarine is of urgent clinical relevance.

KEYWORDS:

Black salve; Bloodroot; Carcinogenesis; Escharotic; Genotoxin; Sanguinaria canadensis; Sanguinarine; Skin cancer; Topical

PMID:
29173498
DOI:
10.1016/j.mrrev.2017.09.001
[Indexed for MEDLINE]
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