title: Cudraxanthone H Induces Growth Inhibition and Apoptosis in Oral Cancer Cells via NF-κB and PIN1 Pathways.
abstract: Cudraxanthone H (CH) is a natural compound isolated from a methanol extract of the root bark of Cudrania tricuspidata, a herbal plant also known as Moraceae. However, the effect of CH on human cancer cells has not been reported previously. The aim of this study was to investigate the anticancer effects and mechanism of action of CH on oral squamous cell carcinoma (OSCC) cells. CH exerted significant antiproliferative effects on OSCC cells in dose- and time-dependent manners. CH also induced apoptosis in OSCC cells, as evidenced by an increased percentage of cells in the sub-G1 phase of the cell cycle, annexin V-positive/propidium iodide-negative cells, and nuclear morphology. This antiproliferative effect of CH was associated with a marked reduction in the expression of cyclin D1 and cyclin E, with a concomitant induction of cyclin-dependent kinase inhibitor (CDKI) expression (p21 and p27). CH inhibited the phosphorylation and degradation of IκB-α and the nuclear translocation of NF-κB p65. Furthermore, CH treatment down-regulated PIN1 mRNA and protein expression in a dose-dependent manner. PIN1 overexpression by infection with adenovirus-PIN1 (Ad-PIN1) attenuated the CH-induced growth-inhibiting and apoptosis-inducing effects, blocked CH-enhanced CDKI expression and restored cyclin levels. In contrast, inhibiting PIN1 expression via juglone exerted the opposite effects. The present study is the first to demonstrate antiproliferative and apoptosis-inducing effects of CH, which exerts its effects by inhibiting NF-κB and PIN1. These data suggest that it might be a novel alternative chemotherapeutic agent for use in the treatment of oral cancer.
authors.affiliation: * Department of Oral and Maxillofacial Pathology, Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Hwa-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: † Department of Oral Anatomy and Developmental Biology, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Seong-Suk
authors.initials: SS
authors.lastname: Jue
authors.affiliation: ‡ Department of Oral Medicine, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Kang
authors.affiliation: * Department of Oral and Maxillofacial Pathology, Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Won-Jung
authors.initials: WJ
authors.lastname: Bae
authors.affiliation: § College of Pharmacy Wonkwang University, Iksan, Republic of Korea.
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: * Department of Oral and Maxillofacial Pathology, Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D006801:Humans; D029586:Moraceae / Q000737:chemistry; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D016328:NF-kappa B / Q000502:physiology*; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000502:physiology*; D008517:Phytotherapy; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics*; D044004:Xanthones / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D044004:Xanthones; C000610436:cudraxanthone H; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase
keywords: Apoptosis; Cudraxanthone H; NF-B; Oral Cancer Cell; PIN1