Gentamicin Induces Selective Toxicity in Metabolically Altered Vemurafenib-Resistant A375 Cells

Fulya Dal Yöntem; Gökhan Ağtürk; Sinem Ayaz; Şeyma Ateşoğlu; Hülya Irmak Aksan; Huri Bulut; Handan Akçakaya; Müfide Aydoğan Ahbab; Ebru Hacıosmanoğlu Aldoğan

Makale detayları

Gentamicin Induces Selective Toxicity in Metabolically Altered Vemurafenib-Resistant A375 Cells

Yazarlar:

Fulya Dal Yöntem | Gökhan Ağtürk | Sinem Ayaz | Şeyma Ateşoğlu | Hülya Irmak Aksan | Huri Bulut | Handan Akçakaya | Müfide Aydoğan Ahbab | Ebru Hacıosmanoğlu Aldoğan

Yayıncı:

Hacettepe University

Ana Başlıklar:

Cell Metabolism | Biochemistry and Cell Biology (Other)

Dergi:

Hacettepe Journal of Biology and Chemistry Vol.52 Issue 3, pp.189-197

Belge Tipi:

Makale

Yayın Tarihi:

1/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001319110

pISSN:

2687-475X

Anahtar kelimeler:

Özet:

 This study investigates the potential repurposing of gentamicin for treating drug-resistant melanoma by targeting metabolic alterations. Rising global cancer incidence and mortality, coupled with the challenge of drug resistance, necessitate novel therapeutic strategies. Initially, we addressed the influence of antibiotics on mitochondrial function, a crucial player in oxidative phosphorylation OXPHOS. To assess this impact, we first cultured two different cancer cells, A375 and PC3, in antibiotic-free medium and showed that mitochondrial membrane potential of cells was increased in the absence of antibiotics compared to cells cultured in antibiotic containing medium. Next, we developed vemurafenib resistance in A375 cells, which were continuously cultured in antibiotic-free medium. The resistant cells exhibited a marked increase in oxygen consumption rate, indicating a shift towards OXPHOS. Finally, we treated these vemurafenib-resistant cells and noncancerous human fibroblast cells CCD-1072Sk with varying concentrations of gentamicin 1-1000 µM. Remarkably, gentamicin showed selective cytotoxicity towards the resistant cells while sparing non-resistant counterparts and noncancerous cells. Our findings highlight gentamicins potential as a therapeutic agent in targeting the metabolic vulnerabilities of drug-resistant melanoma, presenting a viable new pathway in cancer treatment.

 This study investigates the potential repurposing of gentamicin for treating drug-resistant melanoma by targeting metabolic alterations. Rising global cancer incidence and mortality, coupled with the challenge of drug resistance, necessitate novel therapeutic strategies. Initially, we addressed the influence of antibiotics on mitochondrial function, a crucial player in oxidative phosphorylation OXPHOS. To assess this impact, we first cultured two different cancer cells, A375 and PC3, in antibiotic-free medium and showed that mitochondrial membrane potential of cells was increased in the absence of antibiotics compared to cells cultured in antibiotic containing medium. Next, we developed vemurafenib resistance in A375 cells, which were continuously cultured in antibiotic-free medium. The resistant cells exhibited a marked increase in oxygen consumption rate, indicating a shift towards OXPHOS. Finally, we treated these vemurafenib-resistant cells and noncancerous human fibroblast cells CCD-1072Sk with varying concentrations of gentamicin 1-1000 µM. Remarkably, gentamicin showed selective cytotoxicity towards the resistant cells while sparing non-resistant counterparts and noncancerous cells. Our findings highlight gentamicins potential as a therapeutic agent in targeting the metabolic vulnerabilities of drug-resistant melanoma, presenting a viable new pathway in cancer treatment.

 This study investigates the potential repurposing of gentamicin for treating drug-resistant melanoma by targeting metabolic alterations. Rising global cancer incidence and mortality, coupled with the challenge of drug resistance, necessitate novel therapeutic strategies. Initially, we addressed the influence of antibiotics on mitochondrial function, a crucial player in oxidative phosphorylation OXPHOS. To assess this impact, we first cultured two different cancer cells, A375 and PC3, in antibiotic-free medium and showed that mitochondrial membrane potential of cells was increased in the absence of antibiotics compared to cells cultured in antibiotic containing medium. Next, we developed vemurafenib resistance in A375 cells, which were continuously cultured in antibiotic-free medium. The resistant cells exhibited a marked increase in oxygen consumption rate, indicating a shift towards OXPHOS. Finally, we treated these vemurafenib-resistant cells and noncancerous human fibroblast cells CCD-1072Sk with varying concentrations of gentamicin 1-1000 µM. Remarkably, gentamicin showed selective cytotoxicity towards the resistant cells while sparing non-resistant counterparts and noncancerous cells. Our findings highlight gentamicins potential as a therapeutic agent in targeting the metabolic vulnerabilities of drug-resistant melanoma, presenting a viable new pathway in cancer treatment.

 This study investigates the potential repurposing of gentamicin for treating drug-resistant melanoma by targeting metabolic alterations. Rising global cancer incidence and mortality, coupled with the challenge of drug resistance, necessitate novel therapeutic strategies. Initially, we addressed the influence of antibiotics on mitochondrial function, a crucial player in oxidative phosphorylation OXPHOS. To assess this impact, we first cultured two different cancer cells, A375 and PC3, in antibiotic-free medium and showed that mitochondrial membrane potential of cells was increased in the absence of antibiotics compared to cells cultured in antibiotic containing medium. Next, we developed vemurafenib resistance in A375 cells, which were continuously cultured in antibiotic-free medium. The resistant cells exhibited a marked increase in oxygen consumption rate, indicating a shift towards OXPHOS. Finally, we treated these vemurafenib-resistant cells and noncancerous human fibroblast cells CCD-1072Sk with varying concentrations of gentamicin 1-1000 µM. Remarkably, gentamicin showed selective cytotoxicity towards the resistant cells while sparing non-resistant counterparts and noncancerous cells. Our findings highlight gentamicins potential as a therapeutic agent in targeting the metabolic vulnerabilities of drug-resistant melanoma, presenting a viable new pathway in cancer treatment.

Makale detayları

Gentamicin Induces Selective Toxicity in Metabolically Altered Vemurafenib-Resistant A375 Cells

Yazarlar:

Fulya Dal Yöntem | Gökhan Ağtürk | Sinem Ayaz | Şeyma Ateşoğlu | Hülya Irmak Aksan | Huri Bulut | Handan Akçakaya | Müfide Aydoğan Ahbab | Ebru Hacıosmanoğlu Aldoğan

Yayıncı:

Hacettepe University

Ana Başlıklar:

Cell Metabolism | Biochemistry and Cell Biology (Other)

Dergi:

Hacettepe Journal of Biology and Chemistry Vol.52 Issue 3, pp.189-197

Belge Tipi:

Makale

Yayın Tarihi:

1/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001319110

pISSN:

2687-475X

Gentamicin

vemurafenib

melanoma

drug repurposing

Sayı

Makale detayları

Gentamicin Induces Selective Toxicity in Metabolically Altered Vemurafenib-Resistant A375 Cells

Yazarlar: Fulya Dal Yöntem | Gökhan Ağtürk | Sinem Ayaz | Şeyma Ateşoğlu | Hülya Irmak Aksan | Huri Bulut | Handan Akçakaya | Müfide Aydoğan Ahbab | Ebru Hacıosmanoğlu Aldoğan

Yayıncı: Hacettepe University

Ana Başlıklar: Cell Metabolism | Biochemistry and Cell Biology (Other)

Dergi: Hacettepe Journal of Biology and Chemistry Vol.52 Issue 3, pp.189-197

Belge Tipi: Makale

Yayın Tarihi: 1/2024

Belge Dili: İngilizce

Document ID (Org No.): 2001319110

pISSN: 2687-475X

Gentamicin

vemurafenib

melanoma

drug repurposing

Sayı

Yazarlar:

Fulya Dal Yöntem | Gökhan Ağtürk | Sinem Ayaz | Şeyma Ateşoğlu | Hülya Irmak Aksan | Huri Bulut | Handan Akçakaya | Müfide Aydoğan Ahbab | Ebru Hacıosmanoğlu Aldoğan

Yayıncı:

Hacettepe University

Ana Başlıklar:

Cell Metabolism | Biochemistry and Cell Biology (Other)

Dergi:

Hacettepe Journal of Biology and Chemistry Vol.52 Issue 3, pp.189-197

Belge Tipi:

Makale

Yayın Tarihi:

1/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001319110

pISSN:

2687-475X