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Impact of Conventional and Potential New Metal-Based Drugs on Lipid Metabolism in Osteosarcoma MG-63 Cells

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

International journal of molecular sciences, 2023-12, Vol.24 (24), p.17556 [Periódico revisado por pares]

Switzerland: MDPI AG

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Título:
Impact of Conventional and Potential New Metal-Based Drugs on Lipid Metabolism in Osteosarcoma MG-63 Cells
Autor: 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
Assuntos: Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Apoptosis ; Bone cancer ; Bone Neoplasms - drug therapy ; Brain cancer ; Cancer therapies ; Cell growth ; Cell Line, Tumor ; cellular lipophilic extracts ; Cholesterol ; Cisplatin - pharmacology ; Cisplatin - therapeutic use ; Discriminant analysis ; Drugs ; Fatty acids ; human osteosarcoma cells ; Humans ; Ligands ; Lipid Metabolism ; Lipids ; Medical prognosis ; Metabolism ; metabolomics ; NMR ; Nuclear magnetic resonance ; Osteosarcoma - drug therapy ; Osteosarcoma - metabolism ; Ovarian cancer ; Polyamines ; Pt(II) and Pd(II)-complexes ; Sarcoma ; spermine ; Spermine - metabolism ; Statistical analysis
É parte de: International journal of molecular sciences, 2023-12, Vol.24 (24), p.17556
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: This work investigated the mechanisms of action of conventional drugs, cisplatin and oxaliplatin, and the potentially less deleterious drug Pd Spermine (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 Pt Spm maintained control levels; this may reflect enhanced apoptotic behavior for conventional drugs, but not for Pt Spm. Compared to Pt Spm, the more cytotoxic Pd Spm (IC 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, Pd Spm differed from cisplatin in that cells had equivalent (low) levels of triglycerides as Pt Spm, suggesting the absence/low extent of apoptosis. Our results suggest that Pd Spm 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 Pd Spm as a possible cisplatin substitute.
Editor: Switzerland: MDPI AG
Idioma: Inglês

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Impact of Conventional and Potential New Metal-Based Drugs on Lipid Metabolism in Osteosarcoma MG-63 Cells

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

Switzerland: MDPI AG

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