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.

Introduction
 Materials and Methods
  Materials
  Cell culture and luteolin treatment
  MTT assay
  Hoechst staining
  Determination of apoptosis using flow cytometry
  Western blot analysis
  Invasion assay
  Scratch migration assay
  Quantitative PCR
  Statistical analysis
 Results
  Evidence of apoptosis following luteolin treatment of OSCC
  EMT pathway suppression and the inhibition of OSCC-related invasion and migration
 Discussion
 Conclusion
 References

• Jong-Jin Kil(Department of Oral Anatomy, School of Dentistry)
• Bong-Soo Park(Department of Oral Anatomy, School of Dentistry, Pusan National University, BK21 PLUS Project, School of Dentistry, Pusan National University,)
• Hae-Mi Kang(Department of Oral Anatomy, School of Dentistry, Pusan National University, BK21 PLUS Project, School of Dentistry, Pusan National University,)
• Su-Bin Yu(Department of Oral Anatomy, School of Dentistry, Pusan National University, BK21 PLUS Project, School of Dentistry, Pusan National University,)
• Dan-Bi Park(Department of Oral Anatomy, School of Dentistry, Pusan National University, BK21 PLUS Project, School of Dentistry, Pusan National University,)
• Jin-A Park(Department of Oral Anatomy, School of Dentistry, Pusan National University, BK21 PLUS Project, School of Dentistry, Pusan National University,)
• In-Ryoung Kim(Department of Oral Anatomy, School of Dentistry, Pusan National University) Correspondence to