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.

Novel reversible selective inhibitor of CRM1 for targeted therapy in ovarian cancer

“…Cell proliferation was assessed by 5-ethynyl-2′-deoxyuridine (EdU) fluorescence staining using the Cell-Light™ EdU DNA Cell Proliferation Kit (Ruibo Biotech, Guangzhou, China) according to the manufacturer’s instructions [19]. The SKOV-3 cells were seeded in 96-well culture plates and incubated overnight.…”

Kukoamine A inhibits human glioblastoma cell growth and migration through apoptosis induction and epithelial-mesenchymal transition attenuation

“…However, the distinct biological behavior of aggressive proliferation and invasive growth of GBM might be the unexplored therapeutic targets for treatment of this fatal tumor5. Thus, the discovery of new and specific chemotherapeutic agents inhibiting proliferation, migration and invasion of GBM cells are regarded as effective strategies to research and develop new drugs for GBM therapeutics101112131428.…”

“…Thus, inhibiting proliferation, migration and invasion of GBM cells are regarded as effective strategic modalities to screen a new drug for GBM treatment1011121314. Phytochemicals derived from medicinal herbs and dietary plants have recently received much attention as potential therapeutic and preventive agents for cancers, including GBM1516.…”

Novel reversible selective inhibitor of nuclear export shows that CRM1 is a target in colorectal cancer cells

“…After incubation, whole or nuclear cell extracts from treated or untreated cells were subjected to Western blot analyses as described previously. 32 …”