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Cells
Volume 11
Issue 16
10.3390/cells11162482
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Article

Combination of dl922-947 Oncolytic Adenovirus and G-Quadruplex Binders Uncovers Improved Antitumor Activity in Breast Cancer

by
Fabiana Napolitano
1,
Sarah Di Somma
1,
Giuliano Castellano
1,
Jussara Amato
2,
Bruno Pagano
2,
Antonio Randazzo
2,
Giuseppe Portella
1,* and
Anna Maria Malfitano
1,*
1
Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy
2
Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy
*
Authors to whom correspondence should be addressed.
Cells 2022, 11(16), 2482; https://doi.org/10.3390/cells11162482
Submission received: 8 June 2022 / Revised: 2 August 2022 / Accepted: 3 August 2022 / Published: 10 August 2022
(This article belongs to the Special Issue Mechanism of Anti-tumor Immunity of Cells and Immunotherapy)
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Abstract

G-quadruplexes (G4s) are nucleic secondary structures characterized by G-tetrads. G4 motif stabilization induces DNA damage and cancer cell death; therefore, G4-targeting small molecules are the focus of clinical investigation. DNA destabilization induced by G4 ligands might potentiate the anticancer activity of agents targeting DNA or inhibiting its repair such as oncolytic viruses. This study represents the first approach combining G4 ligands, BRACO-19 (B19), pyridostatin (PDS), and the adenovirus dl922-947 in breast cancer cells. We demonstrated that G4 binders and dl922-947 induce cytotoxicity in breast cancer cells (MDA-MB-231 and MCF-7) and at higher doses in other neoplastic cell lines of thyroid (BHT-101 cells) and prostate (PC3 cells). G4 binders induce G4 motifs distributed in the S and G2/M phases in MCF-7 cells. G4 binder/dl922-947 combination increases cell cytotoxicity and the accumulation in subG0/G1. Indeed, G4 binders favor viral entry and replication with no effect on coxsackie and adenovirus receptor. Notably, dl922-947 induces G4 motifs and its combination with PDS potentiates this effect in MCF-7 cells. The agents alone or in combination similarly enhanced cell senescence. Additionally, PDS/dl922-947 combination inactivates STING signaling in MDA-MB-231 cells. Our results suggest that G4 binder/virotherapy combination may represent a novel therapeutic anticancer approach.
Keywords: oncolytic virus; adenovirus; G-quadruplex; breast cancer; senescence; STING oncolytic virus; adenovirus; G-quadruplex; breast cancer; senescence; STING

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MDPI and ACS Style

Napolitano, F.; Di Somma, S.; Castellano, G.; Amato, J.; Pagano, B.; Randazzo, A.; Portella, G.; Malfitano, A.M. Combination of dl922-947 Oncolytic Adenovirus and G-Quadruplex Binders Uncovers Improved Antitumor Activity in Breast Cancer. Cells 2022, 11, 2482. https://doi.org/10.3390/cells11162482

AMA Style

Napolitano F, Di Somma S, Castellano G, Amato J, Pagano B, Randazzo A, Portella G, Malfitano AM. Combination of dl922-947 Oncolytic Adenovirus and G-Quadruplex Binders Uncovers Improved Antitumor Activity in Breast Cancer. Cells. 2022; 11(16):2482. https://doi.org/10.3390/cells11162482

Chicago/Turabian Style

Napolitano, Fabiana, Sarah Di Somma, Giuliano Castellano, Jussara Amato, Bruno Pagano, Antonio Randazzo, Giuseppe Portella, and Anna Maria Malfitano. 2022. "Combination of dl922-947 Oncolytic Adenovirus and G-Quadruplex Binders Uncovers Improved Antitumor Activity in Breast Cancer" Cells 11, no. 16: 2482. https://doi.org/10.3390/cells11162482

APA Style

Napolitano, F., Di Somma, S., Castellano, G., Amato, J., Pagano, B., Randazzo, A., Portella, G., & Malfitano, A. M. (2022). Combination of dl922-947 Oncolytic Adenovirus and G-Quadruplex Binders Uncovers Improved Antitumor Activity in Breast Cancer. Cells, 11(16), 2482. https://doi.org/10.3390/cells11162482

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