title: Plumbagin induces growth inhibition of human glioma cells by downregulating the expression and activity of FOXM1.
abstract: Plumbagin, a natural quinonoid constituent isolated from the root of medicinal plant Plumbago zeylanica L, has exhibited anti-tumor and anti-proliferative activities in various tumor cell lines as well as in animal tumor models. However, its anticancer effects and the mechanisms underlying its suppression of glioma cell growth have not been elucidated. Oncogenic transcription factor Forkhead Box M1 (FOXM1) has garnered particular interest in recent years as a potential target for the prevention and/or therapeutic intervention in glioma, nevertheless, less information is currently available regarding FOXM1 inhibitor. Here, we reported that plumbagin could effectively inhibit cell proliferation, migration and invasion and induce apoptosis of glioma cells. Cell cycle assay showed that plumbagin induced G2/M arrest. Interestingly, we found that plumbagin decreased the expression of FOXM1 both at mRNA level and protein level. Plumbagin also inhibited the transactivation ability of FOXM1, resulting in down-regulating the expression of FOXM1 downstream target genes, such as cyclin D1, Cdc25B, survivin, and increasing the expression of p21(CIP1) and p27(KIP1). Most importantly, down-regulation of FOXM1 by siFOXM1 transfection enhanced plumbagin-induced change in viability. On the contrary, over-expression of FOXM1 by cDNA transfection reduced plumbagin-induced glioma cell growth inhibition. These results suggest that plumbagin exhibits its anticancer activity partially by inactivation of FOXM1 signaling pathway in glioma cells. Our findings indicate that plumbagin may be considered as a potential natural FOXM1 inhibitor, which could contribute to the development of new anticancer agent for therapy of gliomas.
authors.affiliation: Institute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
authors.forename: Mingshan
authors.initials: M
authors.lastname: Niu
authors.forename: Yulong
authors.initials: Y
authors.lastname: Chong
authors.forename: Huize
authors.initials: H
authors.lastname: Liu
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Hu
authors.forename: Dacheng
authors.initials: D
authors.lastname: Wang
authors.forename: Shangfeng
authors.initials: S
authors.lastname: Gao
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shi
authors.forename: Jinxia
authors.initials: J
authors.lastname: Hu
authors.forename: Xiuping
authors.initials: X
authors.lastname: Zhou
authors.forename: Rutong
authors.initials: R
authors.lastname: Yu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D009285:Naphthoquinones / Q000494:pharmacology*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D009285:Naphthoquinones; D034741:RNA, Small Interfering; C014758:plumbagin