Abstract
Nicotine, a tumor promoter in tobacco, can increase Peroxiredoxin (Prx1) and nicotinic acetylcholine receptors (nAChRs) in oral squamous cell carcinoma (OSCC). In the present study, we investigate the effects of nicotine in oral precancerous lesions focusing on apoptosis and nAChR/Prx1 signaling. We detected expression of Prx1, α3nAChR, α7nAChR, phosphorylation of mitogen-activated protein kinases (MAPK) and apoptosis in dysplastic oral keratinocyte (DOK) cells as well as in 4-nitroquinoline 1-oxide (4NQO) or 4NQO + nicotine – induced oral precancerous lesions in Prx1 wild-type (Prx1+/+) and Prx1 knockdown (Prx1+/-) mice. In DOK cells, Prx1 knockdown and blocking α7nAChR activated apoptosis, and nicotine increased the expression of Prx1, α3nAChR and α7nAChR, and inhibited MAPK activation. Moreover, nicotine suppressed apoptosis depending on Prx1 and α7nAChR in DOK cells. In animal bioassay, nicotine and Prx1 promoted growth of 4NQO-induced precancerous lesions in mouse tongue. 4NQO plus nicotine suppressed MAPK activation in Prx1 wild-type mice but not in Prx1 knockdown mice. Our data demonstrate that nicotine inhibits cell apoptosis and promotes the growth of oral precancerous lesions via regulating α7nAChR/Prx1 during carcinogenesis of OSCC.
Highlights
Oral cancer is the sixth most common malignant tumors worldwide, with more than 90% of oral cancers in squamous cell carcinoma type [1]
In oral precancerous cell line dysplastic oral keratinocyte (DOK) cells, nicotine significantly increased the mRNA expression of Peroxiredoxin 1 (Prx1), α3nAChR and α7nAChR when compared to control cells (P < 0.05, Figure 1A)
Prx1 plays an oncogenic role in nicotinerelated oral carcinogenesis
Summary
Oral cancer is the sixth most common malignant tumors worldwide, with more than 90% of oral cancers in squamous cell carcinoma type [1]. A tumor promoter in tobacco, contributes to tumorigenesis mainly by promoting growth and survival of mutated cancer cells and protecting them from apoptosis by creating a tumor favorable environment [6]. The alteration of α7nAChR accompanied by induced epidermal growth factor (EGF), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), cyclin D1, extracellular signal-regulated kinase (ERK1/2) and inhibition of mitochondrial permeability transition pore (mPTP) opening facilitates tumor promotion and progression [13,14,15]. Studies show that long-term use of nicotine enhances cancer cell migration and invasion with morphological alterations, and inhibition of α7nAChR may provide a feasible approach for preventing the progression of head and neck cancer [16]. Α3nAChR is another key acetylcholine receptor in oral epithelial cells. Studies suggest that α3nAChR gene silencing and α3nAChR antagonist inhibit nicotine-induced cell proliferation in oral gingival epithelial cells [17]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
