Anti-proliferative, pro-apoptotic and anti-invasive effect of EC/EV system in human osteosarcoma

Francesca Punzo1,2, Chiara Tortora1,2, Daniela Di Pinto1

  • 1Department of Women, Child and General and Specialist Surgery, Second University of Naples, 80138 Naples, Italy.

Oncotarget
|September 15, 2017
PubMed

Insights

Targeting the Endocannabinoid/Endovanilloid system shows promise for treating osteosarcoma. CB2 receptor stimulation and TRPV1 channel activation reduced tumor cell proliferation and invasion in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Osteosarcoma is a highly aggressive pediatric bone cancer.
  • The Endocannabinoid/Endovanilloid system, including CB1, CB2 receptors, and TRPV1 channels, is a potential anticancer target.
  • Understanding this system's role in osteosarcoma is crucial for developing new therapies.

Purpose of the Study:

  • To investigate the therapeutic potential of CB2 receptor agonist (JWH-133) and TRPV1 channel agonist (RTX) in human osteosarcoma cell lines.
  • To evaluate the effects of these agonists on osteosarcoma cell proliferation, apoptosis, and invasion.
  • To analyze the impact of CB2 and TRPV1 activation on key molecular pathways involved in cancer progression.

Main Methods:

  • Utilized six human osteosarcoma cell lines (MG-63, U-2OS, MNNG/HOS, Saos-2, KHOS/NP, Hs888Lu).
  • Assessed apoptosis and cell migration using specific assays.
  • Quantified gene and protein expression of Caspase-3, AKT, MMP-2, and Notch-1 via Q-PCR and Western Blotting.

Main Results:

  • Both JWH-133 (CB2 agonist) and RTX (TRPV1 agonist) demonstrated significant anti-proliferative and pro-apoptotic effects.
  • Treatment with these agonists led to a marked reduction in cancer cell invasion.
  • CB2 stimulation and TRPV1 activation modulated Caspase-3, AKT, MMP-2, and Notch-1 pathways, achieving similar outcomes.

Conclusions:

  • The Endocannabinoid/Endovanilloid system presents a viable therapeutic target for osteosarcoma.
  • Targeting CB2 receptors or TRPV1 channels can inhibit osteosarcoma progression through shared molecular pathways.
  • These findings support further research into cannabinoid and vanilloid-based therapies for osteosarcoma.

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