Original Article J. Clin. Biochem. Nutr., 46, 60–67, January 2010 StjJ01KOchoC098bryeu.18Bino3grS20N0tn1i-on9a605,cal-40iJl6o/e08aj5Atfcp96ybCratfniloci.0nrle9iFc-ra6el5eBeRioacIdhinceamcliRsteryseaanrscdehNsJuaptraitniyonclin-Dependent ulforaphan re C Kinase Inhibitor, p21 Protein in Human Oral Carcinoma Cells and Nude Mouse Animal Model to Induce G2/M Cell Cycle Arrest Jun-Hee Kim1,*, Ki Han Kwon2,*, Ji-Youn Jung3, Hye-Suk Han1, Jung Hyun Shim1, SeJun Oh1, Kyeong-Hee Choi1, Eun-Sun Choi1, Ji-Ae Shin1, Dae-Ho Leem4, Yunjo Soh5, Nam-Pyo Cho1,** and Sung-Dae Cho1,** 1Department of Oral Pathology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 project, Chonbuk National University, Jeonju, 561-756, Republic of Korea 2Department of Complementary and Alternative Therapy, College of Management, Commerce and Social Welfare, Gwangju University, Gwangju, 503-703, Republic of Korea 3Department of Companion and Laboratory Animal Science, Kongju National University, Yesan, 340-702, Republic of Korea 4Department of Oral and Maxillofacial Surgery, School of Dentistry and Research of Clinical Medicine, Chonbuk National University, Jeonju, 561-756, Republic of Korea 5Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 project, Chonbuk National University, Jeonju, 561-756, Republic of Korea ;?1234R?105aec0cc9eeivpetedd2291.6.7.2.2000099 Received 29 June, 2009; Accepted 21 July, 2009 CopySriugmhtm©a2r0y0? PJCreBvNiously, our group reported that sulforaphane (SFN), a naturally occurring chemopreventive agent from cruciferous vegetables, effectively inhibits the proliferation of KB and YD-10B human oral squamous carcinoma cells by causing apoptosis. In this study, treatment of 20 and 40 µM of SFN for 12 h caused a cell cycle arrest in the G2/M phase. Cell cycle arrest induced by SFN was associated with a significant increase in the p21 protein level and a decrease in cyclin B expression, but there was no change in the cyclin A protein level. In addition, SFN increased the p21 promoter activity significantly. Furthermore, SFN induced p21 protein expression in a nude mouse xenograft model suggesting that SFN is a potent inducer of the p21 protein in human oral squamous carcinoma cells. These findings show that SFN is a promising candidate for molecular-targeting chemotherapy against human oral squamous cell carcinoma. Key Words: Sulforaphane, Human Oral Squamous cell carcinoma, G2/M arrest, p21, cyclin B *Both authors contributed equally to this paper. **To whom correspondence should be addressed. (Sung-Dae Cho) Tel: +82-63-270-4027 Fax: +82-63-270-4025 E-mail: efiwdsc@chonbuk.ac.kr (Nam-Pyo Cho) Tel: +82-63-270-4026 Fax: +82-63-270-4025 E-mail: npcho@chonbuk.ac.kr 60 Introduction The cell cycle is highly regulated by a number of check- point mechanisms, that are essential for the cellular response to stress including DNA damage and abnormal mitogenic signals and the cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors are important factors that regulate the cell cycle progression. However, the checkpoint mechanism does not always work well due to the activation of CDKs