PT  - JOURNAL ARTICLE
AU  - PIOQUINTO-AVILA, ELIZETH
AU  - GONZÁLEZ-CRUZ, ALDO O.
AU  - SOLÍS-ESTRADA, JORGE
AU  - HERNÁNDEZ-JUAREZ, JAVIER
AU  - BALDERAS-RENTERÍA, ISAÍAS
AU  - VILLA-CEDILLO, SHEILA ADELA
AU  - PÉREZ-TRUJILLO, JOSÉ JUAN
AU  - ARREDONDO-ESPINOZA, EDER
TI  - Anticancer Activity of HER2-targeting CPP-PTEN-THP Chimeric Proteins
AID  - 10.21873/anticanres.17062
DP  - 2024 Jun 01
TA  - Anticancer Research
PG  - 2567--2575
VI  - 44
IP  - 6
4099  - http://ar.iiarjournals.org/content/44/6/2567.short
4100  - http://ar.iiarjournals.org/content/44/6/2567.full
SO  - Anticancer Res2024 Jun 01; 44
AB  - Background/Aim: Protein phosphatase and tensin homolog (PTEN) is a tumor suppressor protein with potential to be a new biotechnological drug for PTEN-deficient cancer treatment. This study aimed to develop PTEN-based chimeric proteins (CPP-PTEN-THP) for human epidermal growth factor receptor 2 (HER2)-positive breast cancer treatment, addressing current limitations like inadequate delivery, poor tumor penetration, and low selectivity, while assessing their potential HER2-specific anticancer effects. Materials and Methods: pCEFL-EGFP vector was used for both TAT-PTEN-LTV and KLA-PTEN-LTV construction. Non-contact co-cultures were employed using HEK-293T cells for protein expression, and HCC-1954 and MCF-7 cell lines for cytotoxicity testing. Protein detection was analyzed by western blotting and a docking prediction analysis was performed to infer the interactions. Results: Endogenous and recombinant PTEN protein expression was confirmed in cell lysates. A 54-kDa signal matching the theoretical size of PTEN was detected, showing a greater level in TAT-PTEN-LTV (215.1±26.45%) and KLA-PTEN-LTV (129.2±1.44%) compared to endogenous PTEN. After the noncontact co-culture method, cytotoxic studies showed HCC-1954 preferential cell inhibition growth, with 25.95±0.9% and 12.25±1.29% inhibition by KLA-PTEN-LTV and TAT-PTEN-LTV respectively, compared to MCF-7 cells. An LTV-HER2 interaction model was proposed, inferring that LTV interactions are mainly due to the Pro, Trp, and Tyr residues that target HER2. Conclusion: The developed PTEN-based chimeric proteins have HER2-specific anticancer activity against HCC-1954 cells.