Abstract
Protein kinase B (Akt) plays a very significant role in various cancers including oral cancer. However, it has three isoforms (Akt1, Akt2, and Akt3) and they perform distinct functions and even play contrasting roles in different cancers. Therefore, it becomes essential to evaluate the isoform-specific role of Akt in oral cancer. In the present study, an attempt has been made to elucidate the isoform-specific role of Akt in oral cancer. The immunohistochemical analysis of oral cancer tissues showed an overexpression of Akt1 and 2 isoforms but not Akt3. Moreover, the dataset of “The Cancer Genome Atlas” for head and neck cancer has suggested the genetic alterations of Akt1 and 2 tend to be associated with the utmost poor clinical outcome in oral cancer. Further, treatment of oral cancer cells with tobacco and its components such as benzo(a)pyrene and nicotine caused increased mRNA levels of Akt1 and 2 isoforms and also enhanced the aggressiveness of oral cancer cells in terms of proliferation, and clonogenic and migration potential. Finally, silencing of Akt1 and 2 isoforms caused decreased cell survival and induced cell cycle arrest at the G2/M phase. Akt1/2 silencing also reduced tobacco-induced aggressiveness by decreasing the clonogenic and migration potential of oral cancer cells. Moreover, silencing of Akt1 and 2 isoforms was found to decrease the expression of proteins regulating cancer cell survival and proliferation such as cyclooxygenase-2, B-cell lymphoma 2 (Bcl-2), cyclin D1, and survivin. Thus, the important role of Akt1 and 2 isoforms have been elucidated in oral cancer with in-depth mechanistic analysis.
Highlights
Oral cancer is one of the most challenging diseases faced by mankind, and regardless of several advances made in the field of oral cancer diagnostics and therapeutics, it remains a global health concern.Biomolecules 2019, 9, 253; doi:10.3390/biom9070253 www.mdpi.com/journal/biomoleculesIt was responsible for approximately 145,400 deaths worldwide in the year 2012 [1]
We determined the effect of tobacco and its components such as BAP and nicotine on the expression of Akt isoforms in SAS and KB oral cancer cells
Our results suggest the overexpression of Akt1 and 2 with respect to migration and expression of B-cell lymphoma 2 (Bcl-2), cyclin D1, and survivin proteins, which are important for cancer cell survival and proliferation
Summary
Oral cancer is one of the most challenging diseases faced by mankind, and regardless of several advances made in the field of oral cancer diagnostics and therapeutics, it remains a global health concern.Biomolecules 2019, 9, 253; doi:10.3390/biom9070253 www.mdpi.com/journal/biomoleculesIt was responsible for approximately 145,400 deaths worldwide in the year 2012 [1]. Variations in the incidence of this cancer are the result of several endogenous and exogenous factors such as tobacco use, alcohol intake, and human papilloma virus (HPV) infection. The overall and disease-free survival rates of oral squamous cell carcinoma (OSCC) patients remain unchanged due to high mortality and low cure rate. This is mainly due to the lack of proper diagnostic and therapeutic biomarkers for better diagnosis and prognosis and the lack of effective therapies [8,9,10]
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