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Identification and In Vivo Validation of Unique Anti-Oncogenic Mechanisms Involving Protein Kinase Signaling and

Son Tran1, Patrick Sipila1, Satbir Thakur1

  • 1Department of Oncology, University of Calgary, Calgary, AB T2N 1N4, Canada.

Cancers
|April 27, 2024
PubMed

Insights

PV-10, a rose bengal sodium formulation, shows potent anti-cancer effects by inducing apoptosis and autophagy. This study elucidates its mechanisms against diverse solid tumors, paving the way for future clinical applications.

Area of Science:

  • Oncology
  • Cancer Therapeutics
  • Molecular Biology

Background:

  • PV-10 (rose bengal sodium) exhibits immunotherapeutic and anti-cancer activity.
  • Clinical trials are ongoing for PV-10 in metastatic melanomas and neuroendocrine cancers.
  • Preclinical data on PV-10's mechanisms against diverse adult solid tumors were lacking.

Purpose of the Study:

  • To investigate PV-10's cytotoxic mechanisms in various adult solid tumor cell lines.
  • To explore PV-10's effects on apoptotic and autophagic pathways.
  • To assess PV-10's impact on cancer cell migration and in vivo tumor growth.

Main Methods:

  • Cytotoxicity assays on human breast, colorectal, head and neck, and testicular cancer cell lines.
  • Analysis of apoptotic and autophagic markers (caspase-mediated PARP cleavage, SQSTM1/p62, beclin-1).
  • Wound healing assays for cell migration and in vivo studies in tumor-bearing mice.

Main Results:

  • PV-10 induced cytotoxicity via apoptosis and autophagy, involving caspase-mediated PARP cleavage, SQSTM1/p62 downregulation, and beclin-1 upregulation.
  • PV-10 reduced WNK1 phosphorylation, inhibiting cancer cell migration.
  • Significant tumor growth inhibition was observed in mice treated with PV-10.

Conclusions:

  • PV-10 exhibits anti-cancer activity through apoptosis and autophagy induction.
  • PV-10 impacts cancer cell migration and in vivo tumor progression.
  • Identified mechanisms and biomarkers support future clinical studies of PV-10.
Keywords:
PV-10intralesionalnovel therapeuticsrose bengal sodiumsolid tumorssystemic

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