Chrysophanol inhibits the osteoglycin/mTOR and activats NF2 signaling pathways to reduce viability and proliferation of malignant meningioma cells

ABSTRACT

Chrysophanol shows promising antitumor activity, but how it may work against malignant meningioma is poorly understood. In addition, osteoglycin (OGN) may help mediate the antitumor effects of chrysophanol; thus, this study investigated the potential antitumor mechanism of chrysophanol in malignant meningioma cultures. Meningioma cell line HBL-52 were incubated with varying doses of chrysophanol (0–90 μM) for different time points, and osteoglycin (OGN) was overexpressed or inhibited in some cell cultures to assess its roles. Cell viability was quantified using the CCK8 assay and colony formation assays, while effects on cell cycle distribution and apoptotic rates were examined by flow cytometry and enzyme-linked immunosorbent assays (ELISA) to detect histone DNA levels. Caspase-3 and −9 activities were detected by related commercial kits. Protein expression was assessed using Western blotting. Chrysophanol significantly reduced HBL-52 cell viability, based on reduced colony formation, and proliferation, based on low levels of bromodeoxyuridine incorporation. Annexin V/propidium iodide staining revealed a 30% increase in apoptotic cells at 90 μM chrysophanol (33.7% vs 3.3% in control cultures). Chrysophanol treatment greatly decreased the Bcl-2/Bax expression ratio and increased the expressions of cleaved caspase-3 and −9, and the activities of caspase-3 and −9. Chrysophanol blocked cells in G1 phase and inhibited the OGN/mTOR signaling cascade, but activated neurofibromatosis 2 (NF2) cascade. OGN overexpression activated mTOR, down-regulated NF2, and partially reversed growth inhibition by chrysophanol. Chrysophanol may be useful as a treatment against malignant meningioma by inhibiting OGN/mTOR signaling and activating NF2 signaling.

Graphical Abstract

KEYWORDS:

• Chrysophanol
• malignant meningioma
• apoptosis
• osteoglycin
• mTOR
• nf2

Highlights

• Chrysophanol suppresses the growth of meningioma cells.

• Chrysophanol inhibites OGN/mTOR signaling pathway.

• Chrysophanol activates NF2 signaling.

Disclosure statement

No conflicts of interest.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Notes on contributors

Jiapeng Wang

Jiapeng Wang, MD, works in Department of Intensive Medicine, Suizhou Hospital, Hubei University of Medicine, Suizhou ,Hubei, China.

Peng Lv

Peng Lv, MD, works in Department of Neurosurgery, Suizhou Hospital, Hubei University of Medicine, Suizhou , Hubei,China