Autophagy is a cell survival mechanism that works for the survival of cells under various physiological and pathological conditions. ATG5 is a key protein in the process of autophagy propagation and is involved in tumor development and progression. Chemotherapeutic agents targeting ATG5 enhance the host's immune response in various human cancers and intensify the effectiveness of chemotherapy. However, the physiological role of ATG5 protein in oral squamous cell carcinoma (OSCC) has not been fully recognized. The purpose of this study was to examine the correlation between clinico-pathological factors of OSCC patients and ATG5 immunoexpression through immunohistochemistry (IHC) in the tissues of OSCC patients treated at our hospital, and to analyze the regarding influences and their mechanisms. The authors analyzed 20 OSCC patients from National University Dental Hospital, at Pusan National University from January 2002 to December 2007, which were eligible for the study. Data were obtained by reviewing the medical records of the OSCC patients, and ATG5 immunoexpression was obtained using IHC staining in the tissue samples of the OSCC patients. In the tissue sample of OSCC patients, the immunoexpression of ATG5 elevated, in comparison to the normal oral mucosa, and there was a significant correlation with Drinking, Pathological Stage. In regards to Cox regression analysis, Clinical stage, Tumor size, Histopathologic grade, Cervical nodal metastasis, Loco-regional recurrence, and ATG5 expression have statistically significant correlations. These results imply that the changes in the expression of ATG5 proteins in OSCC can be a prominent factor in the OSCC progression and the prognosis of OSCC patients.

Oral squamous cell carcinoma (OSCC) is the most common type of oral malignancy. Numerous therapies have been proposed for its cure. Research is continually being conducted to develop new forms of treatment as current therapies are associated with numerous side-effects. Luteolin, a common dietary flavonoid, has been demonstrated to possess strong anti-cancer activity against various human cancer cell lines. Nevertheless, research into luteolin-based anticancer activity against oral cancer remains scarce. Thus, the objective of this study was to assess the effect of luteolin as an anti-cancer agent. After treatment with luteolin, Ca9-22 and CAL-27 oral cancer cells showed condensed nuclei and enhanced apoptotic rate with evidence of mitochondria-mediated apoptosis. Epithelial-mesenchymal transition (EMT) is closely related to tumor migration and invasion. Luteolin suppressed cancer cell invasion and migration in the current study. Elevated expression of E-cadherin, an adherens junction protein, was evident in both cell lines after luteolin treatment. Luteolin also significantly inhibited transcription factors (i.e., N-cadherin, Slug, Snail, Twist, and ZEB-1) that regulated expression of tumor suppressors such as E-cadherin based on Western blot analysis and quantitative PCR. Thus, luteolin could induce mitochondrial apoptosis and inhibit cancer cell invasion and migration by suppressing EMT-induced transcription factors.

This study was performed to investigate the correlation between the primary squamous cell carcinoma in oral cavity (POSCC) and paired metastatic oral squamous cell carcinoma in cervical lymph node (MOSCC) via immunohistochemical staining with Ki-67 and p53. The subjects included ten patients (20 specimens) who were diagnosed with OSCC with metastatic lymph nodes from 2010 to 2015 and surgically treated involving neck dissection in Kyungpook National University Hospital. Twenty specimens were stained immunohistochemically with Ki-67 and p53. The degrees of immunostaining by Ki-67 and p53 was evaluated as 0 (no positive cells), weak (1~25% positive cells), moderate (26-50% positive cells) and strong (>50% positive cells). Despite the strong tendency, there was no statistically significant result between expressions of Ki-67 and p53 in POSCC or MOSCC. We found that high expression of Ki-67 was significantly correlated with poor degree of differentiation. Our results suggest that expression of Ki-67 may be a predictable factor for degree of differentiation of POSCC and MOSCC.

Epigallocatechin-3-gallate (EGCG) and theaflavins (TF) are polyphenols included in green and black teas, respectively. Both green and black teas have been studied for their potential health benefits for cancer. Hypoxia-inducible factor (HIF) has been implicated multiple physiological and pathophysiological pathways, particularly, oncogenesis. But, the molecular pathways that govern the cell response to EGCG are not fully elucidated. The present study investigated the intracellular mechanism in oral squamous cell carcinoma (OSCC) cells treated with EGCG, focusing on HIF-1 expression and its effect on epithelial phenotype. EGCG decreased phosphorylated Raf-1 protein in YD 8 OSCC cell, but B-raf protein was not affected at all by EGCG and TF. In addition, we here found that EGCG regulated HIF-1α expression independent of Raf-1 protein. Taken together with our previous result, the result imply that EGCG is attributed to the HIF-1α expression via Raf/MEK/ERK pathway, and the HIF-1α expression is associated with the change of epithelial phenotype in OSCC cell.

It is well known that the imbalance between epithelial cell growth and inhibitor factors may cause human epithelial cancer. Over-expression of the epidermal growth factor receptor(EGFR) has been implicated in the development of oral squamous cell carcinoma. ZD1839 inhibits selectively the EGFR tyrosine kinase activity and is clinically used for cancer patients. However the mechanisms by which it exerts its anti-tumor activity remains unclear. This study attempted to determine the mechanisms underlying the effects of ZD1839 on the cellular level and to characterize the effects of ZD1839 with regard to human oral squamous cell carcinoma(OSCC) cell growth. The YD-10B and YD-38 cell lines established from OSCC in the department of Oral Pathology, Yonsei University College of Dentistry and ZD1839(Iressa) were used for this study. The inhibition of cell proliferation induced by ZD1839 was reversible and the lowest dose of ZD1839 that produced statistically significant growth inhibition in YD cell lines were 0.1 μM. The delay in cell cycle progression was induced by 0.1 μM of ZD1839 treatment after 24 hr. This reduction in cell proliferation and cell cycle delay were associated with up-regulation of the cyclin dependent kinase inhibitor(CDKI), P21CIP1/WAF1 and P27KIP1. Reduced expression of cyclin D1 was also observed after treatment with ZD 1839 to YD-38 cells but not to YD-38. The present results suggest that the antiproliferative effects of ZD1839, in vitro was associated with degradation of cyclin D1, which may be used as a possible indicator of a high cell sensitivity to ZD1839.