Exploring Metabolic Shifts in Kidney Cancer and Non-Cancer Cells Under Pro- and Anti-Apoptotic Treatments Using NMR Metabolomics

resumo

This study investigates the metabolic responses of cancerous (RCC) and non-cancerous (HK2) kidney cells to treatment with Staurosporine (STAU), which has a pro-apoptotic effect, and Bongkrekic acid (BKA), which has an anti-apoptotic effect, individually and in combination, using 1H NMR metabolomics to identify metabolite markers linked to mitochondrial apoptotic pathways. BKA had minimal metabolic effects in RCC cells, suggesting its role in preserving mitochondrial function without significantly altering metabolic pathways. In contrast, STAU induced substantial metabolic reprogramming in RCC cells, disrupting energy production, redox balance, and biosynthesis, thereby triggering apoptotic pathways. The combined treatment of BKA and STAU primarily mirrored the effects of STAU alone, with BKA showing little capacity to counteract the pro-apoptotic effects. In non-cancerous HK2 cells, the metabolic alterations were far less pronounced, highlighting key differences in the metabolic responses of cancerous and non-cancerous cells. RCC cells displayed greater metabolic flexibility, while HK2 cells maintained a more regulated metabolic state. These findings emphasize the potential for targeting cancer-specific metabolic vulnerabilities while sparing non-cancerous cells, underscoring the value of metabolomics in understanding apoptotic and anti-apoptotic mechanisms. Future studies should validate these results in vivo and explore their potential for personalized treatment strategies.

palavras-chave

MITOCHONDRIAL PERMEABILITY TRANSITION; CYTOCHROME-C RELEASE; STAUROSPORINE INDUCES APOPTOSIS; CASPASE ACTIVATION; ATP; INDUCTION; PORE; ADP; TRANSLOCASE; TRANSPORT

categoria

Cell Biology

autores

Trisolini, L; Musio, B; Teixeira, B; Sgobba, MN; Francavilla, AL; Volpicella, M; Guerra, L; De Grassi, A; Gallo, V; Duarte, IF; Pierri, CL

Grupos

G5 - Materiais Biomiméticos, Biológicos e Vivos

Projectos

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)

Rede Nacional de Ressonância Magnética Nuclear (PTNMR)

agradecimentos

This research was supported by EU funding within the MUR PNRR Extended Partnership Initiative on Emerging Infectious Diseases (Project No. PE00000007, INF-ACT) and MUR PNRR National Center for Gene Therapy and Drugs based on RNA Technology (Project No. CN_00000041). The authors are also thankful for the IT resources made available by ReCaS (https://www.recas-bari.it/index.php/en/, accessed on 14 December 2024), a project funded by the MIUR (Italian Ministry for Education, University, and Research) in the "PON Ricerca e Competitivita 2007-2013-Azione I-Interventi di rafforzamento strutturale", PONa3_00052, Avviso 254/Ric, University of Bari. This work also received support from FCT/MCTES to the CICECO-Aveiro Institute of Materials (UIDB/50011/2020, DOI: 10.54499/UIDB/50011/2020; UIDP/50011/2020, DOI: 10.54499/UIDP/50011/2020; LA/P/0006/2020, DOI: 10.54499/LA/P/0006/2020), and LAQV-REQUIMTE (LA/P/0008/202, DOI: 10.54499/LA/P/0008/2020; UIDP/50006/2020, DOI: 10.54499/UIDP/50006/2020; UIDB/50006/2020, DOI: 10.54499/UIDB/50006/2020), through national funds. FCT is also acknowledged for the research contract under the Scientific Employment Stimulus to I.F.D. (CEECIND/02387/2018). The NMR spectrometer is part of the National NMR Network (PTNMR), partially supported by Infrastructure Project No. 022161 (co-financed by FEDER through COMPETE 2020, POCI, and PORL, and FCT through PIDDAC). In addition, the authors would like to thank the Italian Association for Mitochondrial Research-AIRM (https://www.mitoairm.it, accessed on 14 December 2024).