Abstract
STAT3 is a latent transcription factor that plays a vital role in the transmission of extracellular signal from receptors to the nucleus. It has been regarded as a master transcription factor due to its role in the regulation of a broad spectrum of genes, which can contribute to oncogenesis. Persistent activation of STAT3 and deregulation of its signaling has been observed in various human cancers including head and neck squamous cell carcinoma (HNSCC). In the present work, we identified brusatol (BT) as a potential blocker of STAT3 signaling pathway in diverse HNSCC cells. The data from the cell-based experiments suggested that BT-induced cytotoxicity and abrogated the activation of STAT3 and that of upstream kinases such as JAK1, JAK2, and Src. It reduced the levels of nuclear STAT3 and its DNA binding ability. BT treatment increased annexin-V-positive cells, promoted procaspase-3 and PARP cleavage, and downregulated the mRNA and protein expression of diverse proteins (Bcl-2, Bcl-xl, survivin) in HNSCC cells. Taken together, brusatol can function as a promising inhibitor targeting STAT3 signaling pathway in HNSCC.
Highlights
Head and neck cancer is a diverse set of cancers that stems predominantly from the squamous cell lining of mouth, throat, and nose and referred as head and neck squamous cell carcinoma (HNSCC) [1].It accounts for approximately 4% of cancers and over 500,000 new cases are reported annually worldwide [2,3]
We initially explored the effect of BT on the viability in a panel of HNSCC cells such as UMSCC 47, UD SCC2, JMAR, Tu167, LN686, YD-10B, HN-9, and FaDu using MTT assay
The total protein levels of JAK1/2 and Src were not affected. These results indicated that BT induces abrogation of STAT3 signaling by interfering with the activities of all the tested non-receptor tyrosine kinases in UD SCC2, JMAR, YD-10B cells
Summary
Head and neck cancer is a diverse set of cancers that stems predominantly from the squamous cell lining of mouth, throat, and nose and referred as head and neck squamous cell carcinoma (HNSCC) [1].It accounts for approximately 4% of cancers and over 500,000 new cases are reported annually worldwide [2,3]. Head and neck cancer is a diverse set of cancers that stems predominantly from the squamous cell lining of mouth, throat, and nose and referred as head and neck squamous cell carcinoma (HNSCC) [1]. Tobacco chewing, alcohol intake, and human papillomavirus infections are identified as potential risk factors of HNSCC [4]. Surgical procedures such as transoral robotic surgery, laser surgery, and non-surgical options such as radiation therapy along with chemotherapy are the choice of treatment for managing HNSCC [5].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 call
