Simultaneous silencing of lysophosphatidylcholine acyltransferases 1-4 by nucleic acid nanoparticles (NANPs) improves radiation response of melanoma cells

Author(s):Show less -

Saito, Renata F. ^{[1, 2]} ; Rangel, Maria Cristina ^{[1, 2]} ; Halman, Justin R. ^[3] ; Chandler, Morgan ^[3] ; de Sousa Andrade, Luciana Nogueira ^{[1, 2]} ; Odete-Bustos, Silvina ^{[1, 2]} ; Furuya, Tatiane Katsue ^{[1, 2]} ; Murillo Carrasco, Alexis German ^{[1, 2]} ; Chaves-Filho, Adriano B. ^[4] ; Yoshinaga, Marcos Y. ^[4] ; Miyamoto, Sayuri ^[4] ; Afonin, Kirill A. ^[3] ; Chammas, Roger ^{[1, 2, 3]}

Affiliation

^[1] Inst Canc Estado Sao Paulo, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Fac Med, Dept Radiol & Oncol, Ctr Invest Translac Oncol LIM24, Sao Paulo, SP - Brazil

^[3] Univ N Carolina, Dept Chem, Nanoscale Sci Program, Charlotte, NC - USA

^[4] Univ Sao Paulo, Dept Bioquim, Lab Lipideos Modificados, Sao Paulo - Brazil

• Document type: Journal article
• Source: Nanomedicine-Nanotechnology Biology and Medicine; v. 36, AUG 2021.
• Web of Science Citations: 0

Abstract

Radiation induces the generation of platelet-activating factor receptor (PAF-R) ligands, including PAF and oxidized phospholipids. Alternatively, PAF is also synthesized by the biosynthetic enzymes lysophosphatidylcholine acyltransferases (LPCATs) which are expressed by tumor cells including melanoma. The activation of PAF-R by PAF and oxidized lipids triggers a survival response protecting tumor cells from radiation-induced cell death, suggesting the involvement of the PAF/PAF-R axis in radioresistance. Here, we investigated the role of LPCATs in the melanoma cell radiotherapy response. LPCAT is a family of four enzymes, LPCAT1-4, and modular nucleic acid nanoparticles (NANPs) allowed for the simultaneous silencing of all four LPCATs. We found that the in vitro simultaneous silencing of all four LPCAT transcripts by NANPs enhanced the therapeutic effects of radiation in melanoma cells by increasing cell death, reducing long-term cell survival, and activating apoptosis. Thus, we propose that NANPs are an effective strategy for improving radiotherapy efficacy in melanomas. (c) 2021 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 17/50029-6 - The use if RNA-based nano formulations to improve the efficacy of breast cancer treatment and reduce therapy-induced cardiotoxicity
• Grantee: Roger Chammas
• Support Opportunities: Regular Research Grants