Abstract
Oral cancer is a subtype of head and neck cancer which represents 2.65% of all human malignancies. Most of oral cancer is histopathologically diagnosed as oral squamous cell carcinoma (OSCC). OSCC is characterized by a high degree of local invasion and a high rate of metastasis to the cervical lymph nodes. How to prevention and treatment of OSCC is important and imperative. Here, we investigated the therapeutic effect and molecular mechanism of cantharidin, an active compound isolated from blister beetles, on OSCC in vitro. Results showed that cantharidin significantly decreased cell viability in human tongue squamous carcinoma-derived SAS, CAL-27, and SCC-4 cell lines. The further mechanistic studies were carried out in SAS cells. Cantharidin also significantly increased apoptosis-related signals, including caspase-9, caspase-7 and caspase-3 proteins. Besides, cantharidin decreased mitochondrial transmembrane potential (MMP) and induced cytochrome c and apoptosis inducing factor (AIF) release. Cantharidin also increased Bax, Bid, and Bak protein expressions and decreased Bcl-2 protein expression. Cantharidin could also increase the endoplasmic reticulum (ER) stress signals, including the expressions of phosphorylated eIF-2α and CHOP, but not Grp78 and Grp94. Furthermore, cantharidin reduced pro-caspase-12 protein expression. In signals of mitogen-activated protein kinases, cantharidin increased the phosphorylation of JNK, but not ERK and p38. Transfection of shRNA-JNK to OSCC cells effectively reversed the cantharidin-induced cell apoptotic signals, including the mitochondrial and ER stress-related signaling molecules. Taken together, these findings suggest that cantharidin induces apoptosis in OSCC cells via the JNK-regulated mitochondria and ER stress-related signaling pathways.
Highlights
Oral cancer is one of the ten most common malignant human cancers
Our results demonstrated that cantharidin induced both mitochondria and endoplasmic reticulum (ER) stress-related apoptotic signals in oral squamous cell carcinoma (OSCC) cells
These results indicated that cantharidin could activate the apoptotic pathway in OSCC cells
Summary
Oral cancer is one of the ten most common malignant human cancers. the etiology of oral squamous cell carcinoma (OSCC) is not fully understood, the risk factors for carcinogenesis are known to include tobacco use, alcohol, and betel quid chewing [1,2,3,4]. It has been estimated that every year approximately 263,000 new cases of OSCC occur worldwide and 127,000 people die from oral cancer [1, 5]. Development of OSCC has a high potential for rapid and unlimited growth into tumor cells, and correlates with lymph node metastasis and poor 5-year survival rates [1, 7, 8]. It has been reported that the estimated new cases and deaths from lip and oral cavity cancers occurred in 2012 worldwide are 300,400 and 145,400, respectively; the age-standardized oral cavity cancer incidence rates per 100,000 in South-Eastern Asia are 4.0 in males and 2.5 in females [9]. In Taiwan, it has been estimated that the age-standardized incidence rate of OSCC is 146.2 per 100,000 person-years for areca/betel quid chewers [10]. Many studies have explored new therapeutic reagents and possible molecular mechanisms to potentially improve prognosis and therapy for OSCC patients, increasing their life quality and survival rate [1, 12,13,14]
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
