title: β-lapachone suppresses the proliferation of human malignant melanoma cells by targeting specificity protein 1.
abstract: β-lapachone (β-lap), a novel natural quinone derived from the bark of the Pink trumpet tree (Tabebuia avellanedae) has been demonstrated to have anticancer activity. In this study, we investigated whether β-lap exhibits anti-proliferative effects on two human malignant melanoma (HMM) cell lines, G361 and SK-MEL-28. The effects of β-lap on the HMM cell lines were investigated using 3-(4,5-dimethylthiazol-2-yl)‑5-(3-carboxymethoxyphenyl)‑2-(4-sulfophenyl-2H-tetrazolium (MTS) assay, 4',6-diamidino-2-phenylindole (DAPI) staining, Annexin V and Dead cell assay, mitochondrial membrane potential (MMP) assay and western blot analysis. We demonstrated that β-lap significantly induced apoptosis and suppressed cell viability in the HMM cells. Intriguingly, the transcription factor specificity protein 1 (Sp1) was significantly downregulated by β-lap in a dose- and time-dependent manner. Furthermore, β-lap modulated the protein expression level of the Sp1 regulatory genes including cell cycle regulatory proteins and apoptosis-associated proteins. Taken together, our findings indicated that β-lap modulates Sp1 transactivation and induces apoptotic cell death through the regulation of cell cycle- and apoptosis-associated proteins. Thus, β-lap may be used as a promising anticancer drug for cancer prevention and may improve the clinical outcome of patients with cancer.
authors.affiliation: Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors.forename: Woong
authors.initials: W
authors.lastname: Bang
authors.affiliation: Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Jeon
authors.affiliation: Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors.forename: Ra Ham
authors.initials: RH
authors.lastname: Lee
authors.affiliation: Pohang Center for Evaluation of Biomaterials, Pohang, Gyeongbuk 790‑834, Republic of Korea.
authors.forename: Seon-Min
authors.initials: SM
authors.lastname: Park
authors.affiliation: Pohang Center for Evaluation of Biomaterials, Pohang, Gyeongbuk 790‑834, Republic of Korea.
authors.forename: Jae-Cheon
authors.initials: JC
authors.lastname: Shin
authors.affiliation: Department of Animal Science, College of Agricultural and Life Science, Chonbuk National University, Jeonju 561‑756, Republic of Korea.
authors.forename: Nag-Jin
authors.initials: NJ
authors.lastname: Choi
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea.
authors.forename: Jung-Jae
authors.initials: JJ
authors.lastname: Cho
authors.affiliation: Department of Prosthodontics, School of Dentistry and Institute of Oral Bio-Science and Research Institute of Clinical Medicine, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Seo
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors.forename: Seung-Yeop
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea.
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Shim
authors.affiliation: Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Chae
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D008545:Melanoma / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009285:Naphthoquinones / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D012878:Skin Neoplasms / Q000473:pathology*; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009285:Naphthoquinones; D009363:Neoplasm Proteins; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; C014638:beta-lapachone