title: Anti-proliferative effect of honokiol in oral squamous cancer through the regulation of specificity protein 1.
abstract: Honokiol (HK), a novel plant-derived natural product, is a physiologically activated compound with polyphenolic structure, and has been identified to function as an anticancer agent. It has been widely used in several diseases as a traditional medicine for a long time. We investigated whether HK could show anticancer effects on two oral squamous cell lines (OSCCs), HN-22 and HSC-4. We demonstrated that HK-treated cells showed dramatic reduction in cell growth and apoptotic cell morphologies. Intriguingly, the transcription factor specificity protein 1 (Sp1) was significantly inhibited by HK in a dose-dependent manner. Furthermore, we checked changes in cell cycle regulatory proteins and anti-apoptotic proteins at the molecular level, which are known as Sp1 target genes. The important key regulators in the cell cycle such as p27 and p21 were up-regulated by HK-mediated down-regulation of Sp1, whereas anti-apoptotic proteins including Mcl-1 and survivin were decreased, resulting in caspase-dependent apoptosis. Taken together, results from this study suggest that HK could modulate Sp1 transactivation and induce apoptotic cell death through the regulation of cell cycle and suppression of anti‑apoptotic proteins. In addition, HK may be used in cancer prevention and therapies to improve the clinical outcome as an anticancer drug.
authors.affiliation: Department of Oral Pharmacology, School of Dentistry and Institute of Dental Bioscience, BK21 project, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Seon Mi
authors.initials: SM
authors.lastname: Ko
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Young-Woock
authors.initials: YW
authors.lastname: Noh
authors.forename: Nag-Jin
authors.initials: NJ
authors.lastname: Choi
authors.forename: Sung-Dae
authors.initials: SD
authors.lastname: Cho
authors.forename: Hong Seop
authors.initials: HS
authors.lastname: Moon
authors.forename: Young Sik
authors.initials: YS
authors.lastname: Cho
authors.forename: Jae-Chen
authors.initials: JC
authors.lastname: Shin
authors.forename: Seon-Min
authors.initials: SM
authors.lastname: Park
authors.forename: Kang Seok
authors.initials: KS
authors.lastname: Seo
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Chae
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Shim
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000008:administration & dosage* / Q000737:chemistry; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017705:Lignans / Q000008:administration & dosage* / Q000737:chemistry; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010944:Plants / Q000737:chemistry; D016329:Sp1 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D017705:Lignans; D016329:Sp1 Transcription Factor; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols