Academic Journal
Impact of Conventional and Potential New Metal-Based Drugs on Lipid Metabolism in Osteosarcoma MG-63 Cells
| العنوان: | Impact of Conventional and Potential New Metal-Based Drugs on Lipid Metabolism in Osteosarcoma MG-63 Cells |
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| المؤلفون: | Bispo, Daniela S. C., Correia, Marlene, Carneiro, Tatiana J., Martins, Ana S., Reis, Aliana A. N., Carvalho, Ana L. M. Batista de, Marques, Maria P. M., Gil, Ana M. |
| بيانات النشر: | MDPI |
| سنة النشر: | 2023 |
| المجموعة: | Repositório Institucional da Universidade de Aveiro (RIA) |
| مصطلحات موضوعية: | Pt(II) and Pd(II)-complexes, spermine, human osteosarcoma cells, NMR, metabolomics, cellular lipophilic extracts |
| الوصف: | This work investigated the mechanisms of action of conventional drugs, cisplatin and oxaliplatin, and the potentially less deleterious drug Pd2Spermine (Spm) and its Pt(II) analog, against osteosarcoma MG-63 cells, using nuclear-magnetic-resonance metabolomics of the cellular lipidome. The Pt(II) chelates induced different responses, namely regarding polyunsaturated-fatty-acids (increased upon cisplatin), suggesting that cisplatin-treated cells have higher membrane fluidity/permeability, thus facilitating cell entry and justifying higher cytotoxicity. Both conventional drugs significantly increased triglyceride levels, while Pt2Spm maintained control levels; this may reflect enhanced apoptotic behavior for conventional drugs, but not for Pt2Spm. Compared to Pt2Spm, the more cytotoxic Pd2Spm (IC50 comparable to cisplatin) induced a distinct phospholipids profile, possibly reflecting enhanced de novo biosynthesis to modulate membrane fluidity and drug-accessibility to cells, similarly to cisplatin. However, Pd2Spm differed from cisplatin in that cells had equivalent (low) levels of triglycerides as Pt2Spm, suggesting the absence/low extent of apoptosis. Our results suggest that Pd2Spm acts on MG-63 cells mainly through adaptation of cell membrane fluidity, whereas cisplatin seems to couple a similar effect with typical signs of apoptosis. These results were discussed in articulation with reported polar metabolome adaptations, building on the insight of these drugs' mechanisms, and particularly of Pd2Spm as a possible cisplatin substitute. ; This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 (doi:10.54499/UIDB/50011/2020), UIDP/50011/2020 (doi:10.54499/UIDP/50011/2020) and LA/P/0006/2020 (doi:10.54499/LA/P/0006/2020) (AMG), financed by national funds through the FCT/MCTES (PIDDAC). We also acknowledge funds from POCentro, Portugal 2020, and European Community through the FEDER, and by the Portuguese Foundation for Science and Technology (FCT) through ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1661-6596 1422-0067 |
| Relation: | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50011%2F2020/PT; info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F50011%2F2020/PT; info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0006%2F2020/PT; info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50006%2F2020/PT; info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00070%2F2020/PT; info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F00070%2F2020/PT; PO-CI-01-0145-FEDER-0016786; info:eu-repo/grantAgreement/FCT/3599-PPCDT/2022.04286.PTDC/PT; N-022161; info:eu-repo/grantAgreement/FCT/OE/SFRH%2FBD%2F150655%2F2020/PT; info:eu-repo/grantAgreement/FCT/OE/SFRH%2FBD%2F145920%2F2019/PT; SFRH/BD/ 111576/2015; https://www.mdpi.com/1422-0067/24/24/17556; http://hdl.handle.net/10773/40132; 17556 |
| DOI: | 10.3390/ijms242417556 |
| الاتاحة: | http://hdl.handle.net/10773/40132 https://doi.org/10.3390/ijms242417556 |
| Rights: | openAccess ; https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.7E9012CB |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 16616596 14220067 |
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| DOI: | 10.3390/ijms242417556 |