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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
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Anticancer Activity of HER2-targeting CPP-PTEN-THP Chimeric Proteins

Elizeth Pioquinto-Avila1, Aldo O González-Cruz1, Jorge Solís-Estrada1

  • 1Laboratorio de Farmacología Molecular y Modelos Biológicos, Facultad de Ciencias Químicas, Universidad Autonoma de Nuevo Leon, UANL, Nuevo León, México.

Anticancer Research
|May 31, 2024
PubMed
Abstract

Insights

New chimeric proteins based on the tumor suppressor Protein Phosphatase and Tensin homolog (PTEN) show specific anticancer effects against HER2-positive breast cancer cells. These engineered PTEN proteins demonstrate targeted delivery and inhibition of cancer cell growth.

Area of Science:

  • Biotechnology
  • Oncology
  • Molecular Biology

Background:

  • Protein Phosphatase and Tensin homolog (PTEN) is a crucial tumor suppressor.
  • PTEN deficiency is implicated in various cancers, presenting a target for therapeutic development.
  • Current limitations in cancer drug delivery include poor tumor penetration and low selectivity.

Purpose of the Study:

  • To engineer PTEN-based chimeric proteins (CPP-PTEN-THP) for targeted therapy.
  • To evaluate the efficacy of these proteins against human epidermal growth factor receptor 2 (HER2)-positive breast cancer.
  • To assess the HER2-specific anticancer effects and delivery capabilities of the developed proteins.

Main Methods:

  • Construction of chimeric proteins TAT-PTEN-LTV and KLA-PTEN-LTV using the pCEFL-EGFP vector.
  • Protein expression confirmed via western blotting in HEK-293T cells.
  • Cytotoxicity assays using non-contact co-cultures of HCC-1954 (HER2-positive) and MCF-7 cell lines.

Main Results:

  • Successful expression of recombinant PTEN chimeric proteins, with elevated levels compared to endogenous PTEN.
  • Preferential inhibition of HCC-1954 cell growth by KLA-PTEN-LTV (25.95±0.9%) and TAT-PTEN-LTV (12.25±1.29%).
  • Docking analysis suggested specific interactions between the LTV moiety and HER2, mediated by Pro, Trp, and Tyr residues.

Conclusions:

  • The developed PTEN-based chimeric proteins exhibit HER2-specific anticancer activity.
  • These engineered proteins show potential for targeted therapy in HER2-positive breast cancer.
  • The findings support the therapeutic potential of chimeric PTEN proteins for cancer treatment.
Keywords:
Cell-penetrating peptideHER2-positive breast cancerPTENnoncontact coculturetargeted therapytumor-homing peptide

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