P-MAPA and IL-12 Differentially Regulate Proteins Associated with Ovarian Cancer Progression: A Proteomic Study

Author(s)

Lupi Junior, Luiz Antonio ^[1] ; Cucielo, Maira Smaniotto ^[1] ; Domeniconi, Raquel Fantin ^[1] ; dos Santos, Lucilene Delazari ^[2] ; Silveira, Henrique Spaulonci ^[1] ; Nunes, Iseu da Silva ^[3] ; Martinez, Marcelo ^[4] ; Martinez, Francisco Eduardo ^[1] ; Favaro, Wagner Jose ^[5] ; de Almeida Chuffa, Luiz Gustavo ^[1]

Affiliation

^[1] Univ Estadual Paulista, Dept Anat, Inst Biosci, UNESP, BR-18618689 Botucatu, SP - Brazil

^[2] Univ Estadual Paulista, Ctr Study Venoms & Venomous Anim CEVAP, UNESP, BR-18618689 Botucatu, SP - Brazil

^[3] Farmabrasilis R&D Div, BR-18610307 Campinas, SP - Brazil

^[4] Univ Fed Sao Carlos, Dept Morphol & Pathol, BR-13565905 Sao Carlos, SP - Brazil

^[5] Univ Estadual Campinas, Dept Struct & Funct Biol, UNICAMP, BR-13083970 Campinas, SP - Brazil

• Document type: Journal article
• Source: ACS OMEGA; v. 4, n. 26, p. 21761-21777, DEC 24 2019.
• Web of Science Citations: 0

Abstract

To investigate the potential role of immunotherapies in the cellular and molecular mechanisms associated with ovarian cancer (OC), we applied a comparative proteomic toll using protein identification combined with mass spectrometry. Herein, the effects of the protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride, known as P-MAPA, and the human recombinant interleukin-12 (hrIL-12) were tested alone or in combination in human SKOV-3 cells. The doses and period were defined based on a previous study, which showed that 25 mu g/mL P-MAPA and 1 ng/mL IL-12 are sufficient to reduce cell metabolism after 48 h. Indeed, among 2,881 proteins modulated by the treatments, 532 of them were strictly concordant and common. P-MAPA therapy upregulated proteins involved in tight junction, focal adhesion, ribosome constitution, GTP hydrolysis, semaphorin interactions, and expression of SLIT and ROBO, whereas it downregulated ERBB4 signaling, toll-like receptor signaling, regulation of NOTCH 4, and the ubiquitin proteasome pathway. In addition, IL-12 therapy led to upregulation of leukocyte migration, tight junction, and cell signaling, while cell communication, cell metabolism, and Wnt signaling were significantly downregulated in OC cells. A clear majority of proteins that were overexpressed by the combination of P-MAPA with IL-12 are involved in tight junction, focal adhesion, DNA methylation, metabolism of RNA, and ribosomal function; only a small number of downregulated proteins were involved in cell signaling, energy and mitochondrial processes, cell oxidation and senescence, and Wnt signaling. These findings suggest that P-MAPA and IL-12 efficiently regulated important proteins associated with OC progression; these altered proteins may represent potential targets for OC treatment in addition to its immunoadjuvant effects. (AU)

• FAPESP's process: 16/03993-9 - Effect of P-MAPA immunomodulator associated to interleukin-12 on Ovarian Cancer: in vitro and in vivo approaches involving the inflammatory process and immune system
• Grantee: Luiz Gustavo de Almeida Chuffa
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/00906-6 - Melatonin and the MT1 and MT2 receptors: effects on apoptosis, cell proliferation and migratory potential of the ovarian carcinoma cells (SKOV-3 cell line)
• Grantee: Luiz Gustavo de Almeida Chuffa
• Support Opportunities: Regular Research Grants