Suppression of ERK/NF-κB Activation Is Associated With Amentoflavone-Inhibited Osteosarcoma Progression In Vivo

Yen-Ju Lee1,2, Jing-Gung Chung3,4, Yi-Ting Chien5

  • 1Department of Emergency Medicine, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan, R.O.C.

Anticancer Research
|July 3, 2019
PubMed
Abstract

Insights

Amentoflavone effectively inhibits osteosarcoma (OS) tumor growth in vivo. This natural compound reduces key proteins involved in cancer progression by inhibiting the ERK/NF-κB signaling pathway.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Osteosarcoma (OS) is a primary bone cancer with high metastatic potential.
  • Amentoflavone, a natural flavonoid, has shown promise in inhibiting OS cell metastasis in vitro.
  • Further investigation is needed to confirm its efficacy and mechanism in vivo.

Purpose of the Study:

  • To evaluate the antitumoral efficacy of amentoflavone in an in vivo osteosarcoma model.
  • To elucidate the molecular mechanisms underlying amentoflavone's inhibitory effects on osteosarcoma progression.

Main Methods:

  • Amentoflavone (100 mg/kg/day) or vehicle control was administered to mice with U-2 OS osteosarcoma xenografts for 15 days.
  • Tumor growth was monitored using digital calipers and bioluminescence imaging (BLI).
  • Signal transduction and protein expression (P-ERK, NF-κB, VEGF, MMP-9, XIAP, cyclin-D1) were assessed via western blotting.

Main Results:

  • Amentoflavone significantly suppressed osteosarcoma tumor growth in vivo.
  • Treatment reduced protein levels of phospho-extracellular signal-regulated kinase (P-ERK), nuclear factor-kappaB (NF-κB) p65, vascular endothelial growth factor (VEGF), matrix metallopeptidase 9 (MMP-9), X-linked inhibitor of apoptosis protein (XIAP), and cyclin-D1.
  • These findings suggest amentoflavone impacts multiple pathways crucial for tumor progression.

Conclusions:

  • Amentoflavone demonstrates significant in vivo antitumoral efficacy against osteosarcoma.
  • The observed inhibition of osteosarcoma progression is linked to the suppression of ERK/NF-κB signaling pathways.
  • Amentoflavone represents a potential therapeutic agent for osteosarcoma treatment.

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