The Role of Nitrosamine (NNK) in Breast Cancer Carcinogenesis

Abstract

Smoking cigarettes is one of the most concerning issues that leads to tobacco-related cancers and can even result in death. Therefore, these issues should be addressed with a great sense of urgency with low-cost and simple approaches. Over the past several years, the scientific community has attempted to find solutions to overcome this issue. Thus, a large number of excellent studies have been reported in this field, and summarizing these results and providing important roadmaps for future studies is currently of great importance. Finding an outstanding solution to address aforementioned issue would be of great value to the community and to the social. Tobacco contains thousands of chemicals, and sixty-nine compounds have been established as human carcinogens; specifically, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the strongest carcinogen among the tobacco-specific nitrosamines. Tobacco carcinogens are also linked to mammary gland pathogenesis and increased risk of developing many cancers, including breast cancer, the most common cancer in women worldwide. This mini-review summarizes the role of NNK and the mechanisms of its receptor, nicotine acetylcholine receptor (nAChR), signaling in breast cancer based on publications identified using the keywords "secondhand smoke (SHS)", "Nitrosamines" and "breast cancer". Furthermore, this review considers the risk of NNK to the public in an effort to reduce exposure to SHS in women and their chances of developing breast cancer.

Keywords: Breast cancer; Nicotinic acetylcholine receptor; Nitrosamines; Second hand smoke.

Fig. 1

The structures of the nitrosoamines found in tobacco smoke. NNN (N-nitrosonornicotine), NAT (N-nitrosoanatabine), NAB (N-nitrosoanabasine), NNK (4-methylnitrosamino-1-3-pyridyl-1-butanone), NDMA (N-nitrosodimethylamine), NMEA (N-nitrosomethylamin), NDELA (N-Nitrosodiethanolamine), NSAR (N-nitrososarcosine), NPIP (N-nitrosopiperidine), NPYR (N-nitrosopyrrolidine), NDEA (N-nitrosodiethylamine), NMOR (N-nitrosomorpholine)

Fig. 2

α9nAChR involved signal pathway in breast cancer. The three abundant α subunits expressed in breast tissue are able to form one homopentameric nAChR (α9nAChR) and two possible heteropentameric structures (α9α10-, α9α5-) of nAChRs. NNK and nicotine with estrogen stimulation can activate downstream transcription factors, AP1 and VDR through the PI3K/Akt and MAPK signaling pathways. The activation of AP1 and VDR transcription factors has been known by association with various cancer phenotypes including cell proliferation and migration. Binding of these transcription factors on the promoter region of α9-nAChR leads to a strong positive feedback loop