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Ponicidin inhibited gallbladder cancer proliferation and metastasis by decreasing MAGEB2 expression through FOXO4

Study · animal · Phytomedicine : international journal of phytotherapy and phytopharmacology · 2023 · DOI 10.1016/j.phymed.2023.154785 · PMID 37002972

Plain-language summary

Paraphrased from the published abstract below — not a verdict on whether anything works.

This study examined ponicidin, a diterpenoid compound from the herb Rabdosia rubescens, in gallbladder cancer (GBC) cell lines and a nude mouse model. Using CCK-8, colony formation, EdU-488, invasion/migration, and wound-healing assays along with mRNA sequencing, Western blot, immunohistochemistry, ChIP, and dual-luciferase assays, the authors report that ponicidin reduced proliferation, invasion, and migration of GBC cells in vitro, associated with downregulation of MAGEB2 expression via upregulated nuclear FOXO4 that inhibited MAGEB2 transcription. In the nude mouse model of GBC, ponicidin administration was associated with reduced tumor growth. The authors describe ponicidin as a candidate agent for further study in GBC.

Abstract

Gallbladder cancer (GBC) is the most aggressively malignant tumor in the bile duct system. The prognosis for patients with GBC is extremely poor. Ponicidin is a diterpenoid compound extracted and purified from the traditional Chinese herb Rabdosia rubescens, and showed promising anti-cancer effects in a variety of tumors. However, Ponicidin has not been investigated in GBC. CCK-8, colony formation assay and EdU-488 DNA synthesis assay were performed to investigate the effect of Ponicidin on GBC cells proliferation. Cell invasion and migration assays and wound-healing assay were used to explore the effect of Ponicidin on invasion and migration ability of GBC cells. mRNA-seq was adopted to explore the underlying mechanisms. Western blot and immunohistochemical staining were conducted to detect the protein level. CHIP assay and dual-luciferase assay were used to validate binding motif. Nude mouse model of GBC was used to assess the anti-tumor effect and safety of Ponicidin. Ponicidin inhibited the proliferation and cell invasion and migration of GBC cells in vitro. Moreover, Ponicidin exerted anti-tumor effects by down-regulating the expression of MAGEB2. Mechanically, Ponicidin upregulated the FOXO4 expression and promoted it to accumulate in nucleus to inhibit the transcript of MAGEB2. Furthermore, Ponicidin suppressed tumor growth in the nude mouse model of GBC with excellent safety. Ponicidin may be a promising agent for the treatment of GBC effectively and safely.

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