Heang-Eun Lee1, Eun-Sun Choi1, Ji-Youn Jung2, Myung-Jo You3, Lee-Han Kim4, Sung-Dae Cho5. 1. Department of Oral Pathology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University, JeonJu 561-756, Republic of Korea. 2. Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 314-701, Republic of Korea. 3. Laboratory of Veterinary Parasitology, College of Veterinary Medicine and Bio-Safety Research Centre, Chonbuk National University, Jeonju 561-756, Republic of Korea. 4. Division of Life Sciences, Wonkwang University, Iksan 570-749, Republic of Korea. 5. Department of Oral Pathology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University, JeonJu 561-756, Republic of Korea. Electronic address: efiwdsc@chonbuk.ac.kr.
Abstract
OBJECTIVES: Dibenzylideneacetone (DBA), a curcumin analogue that has anti-cancer activity in a variety of tumor cells. In this study, we investigated the apoptotic effects of DBA and its molecular mechanism in human mucoepidermoid carcinoma (MEC) cell lines and tumor xenografts. MATERIAL AND METHODS: The apoptotic effects and related molecular mechanisms of DBA on MEC cell lines were evaluated using cell viability assay, DAPI staining, Western blot analysis, reverse transcriptase-polymerase chain reaction (RT-PCR) and Dual-luciferase Reporter Assay. The anti-tumor activity using in vivo were determined by Nude mouse xenograft assay and histopathological examination. RESULTS: DBA decreased cell viability and induced apoptosis in MEC cells. These events were accompanied by inhibition of specificity protein 1 (Sp1). DBA did not induce major changes in Sp1 mRNA and promoter activity. Furthermore, inhibition of protein synthesis by cycloheximide demonstrated that DBA decreased Sp1 protein stability, but DBA did not attenuate phosphorylation of eIF4E. DBA also increased Bim and truncated Bid (t-Bid) via Sp1. Finally, DBA exhibited significant anti-tumor activity in athymic nude mice xenografts bearing MC-3 cells by regulating Sp1, Bim and t-Bid without any systemic toxicity. CONCLUSION: These results elucidate a crucial apoptotic mechanism of DBA and suggest that DBA may be a potent anticancer drug candidate for MEC.
OBJECTIVES:Dibenzylideneacetone (DBA), a curcumin analogue that has anti-cancer activity in a variety of tumor cells. In this study, we investigated the apoptotic effects of DBA and its molecular mechanism in humanmucoepidermoid carcinoma (MEC) cell lines and tumor xenografts. MATERIAL AND METHODS: The apoptotic effects and related molecular mechanisms of DBA on MEC cell lines were evaluated using cell viability assay, DAPI staining, Western blot analysis, reverse transcriptase-polymerase chain reaction (RT-PCR) and Dual-luciferase Reporter Assay. The anti-tumor activity using in vivo were determined by Nude mouse xenograft assay and histopathological examination. RESULTS:DBA decreased cell viability and induced apoptosis in MEC cells. These events were accompanied by inhibition of specificity protein 1 (Sp1). DBA did not induce major changes in Sp1 mRNA and promoter activity. Furthermore, inhibition of protein synthesis by cycloheximide demonstrated that DBA decreased Sp1 protein stability, but DBA did not attenuate phosphorylation of eIF4E. DBA also increased Bim and truncated Bid (t-Bid) via Sp1. Finally, DBA exhibited significant anti-tumor activity in athymic nude mice xenografts bearing MC-3 cells by regulating Sp1, Bim and t-Bid without any systemic toxicity. CONCLUSION: These results elucidate a crucial apoptotic mechanism of DBA and suggest that DBA may be a potent anticancer drug candidate for MEC.