title: Downregulation of Sp1 is involved in honokiol-induced cell cycle arrest and apoptosis in human malignant pleural mesothelioma cells.
abstract: Malignant pleural mesothelioma (MPM) is an extremely aggressive type of cancer and is associated with a poor patient prognosis due to its rapid progression. Novel therapeutic agents such as honokiol (HNK) improve the clinical outcomes of cancer therapy, yet the mechanisms involved have not been fully elucidated. The present study examined the regulatory effects of HNK on the growth and apoptosis of MSTO-211H mesothelioma cells and investigated its anticancer mechanism. The results revealed that HNK significantly reduced the cell viability and increased the sub-G1 population in MSTO-211H cells and suppressed the expression of the specificity protein 1 protein (Sp1). HNK reduced the transcriptional activity of Sp1 regulatory proteins, including cyclin D1, Mcl-1 and survivin, and, thus, induced apoptosis signaling pathways by increasing Bax, reducing Bid and Bcl-xl and activating caspase-3 and PARP in mesothelioma cells. The results suggest that Sp1, a novel molecular target of HNK, may be related to cell cycle arrest and apoptosis induction through the modulation of signal transduction pathways in MPM.
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, Brain Korea 21 Project, Chonbuk National University, Jeonju 561‑756, Republic of Korea.
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Chae
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Shim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008654:Mesothelioma; D010997:Pleural Neoplasms; D015398:Signal Transduction; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D001713:Biphenyl Compounds; D018797:Cell Cycle Proteins; D017705:Lignans; D016329:Sp1 Transcription Factor; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols