title: Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer.
abstract: Cervical cancer is the third most common cancer and the third leading cause of death among women. However, the standard treatment for cervical cancer includes cisplatin, which can cause side effects such as hematological damage or renal toxicity. New innovations in cervical cancer treatment focus on developing more effective and better-tolerated therapies such as Sp1-targeting drugs. Previous studies suggested that mithramycin A (Mith) inhibits the growth of various cancers by decreasing Sp1 protein. However, how Sp1 protein is decreased by Mith is not clear. Few studies have investigated the regulation of Sp1 protein by proteasome-dependent degradation as a possible control mechanism for the regulation of Sp1 in cancer cells. Here, we show that Mith decreased Sp1 protein by inducing proteasome-dependent degradation, thereby suppressing cervical cancer growth through a DR5/caspase-8/Bid signaling pathway. We found that prolonged Mith treatment was well tolerated after systemic administration to mice carrying cervical cancer cells. Reduction of body weight was minimal, indicating that Mith was a good therapeutic candidate for treatment of cancers in which Sp1 is involved in promoting and developing disease.
authors.affiliation: Division of High-risk Pathogen Research, Korea Centers for Disease Control and Prevention, Osong, Republic of Korea.
authors.forename: Eun-Sun
authors.initials: ES
authors.lastname: Choi
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Graduate School of Medicine, Incheon 406-840, Korea.
authors.forename: Jeong-Seok
authors.initials: JS
authors.lastname: Nam
authors.affiliation: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 314-701, Republic of Korea.
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Jung
authors.affiliation: Department of Oral Pathology, School of Dentistry and Institute of Biodegradable Material, Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University, Jeon-ju 561-756, Republic of Korea.
authors.forename: Nam-Pyo
authors.initials: NP
authors.lastname: Cho
authors.affiliation: Department of Oral Pathology, School of Dentistry and Institute of Biodegradable Material, Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University, Jeon-ju 561-756, Republic of Korea.
authors.forename: Sung-Dae
authors.initials: SD
authors.lastname: Cho
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D008926:Plicamycin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D034622:RNA Interference; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000903:Antibiotics, Antineoplastic; D051023:BH3 Interacting Domain Death Agonist Protein; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; C066851:mithramycin A; D010447:Peptide Hydrolases; D053181:Caspase 8; D008926:Plicamycin