Cover Story Current Issue

Alterations in mitochondrial structure and function are commonly observed in adult-onset neurodegenerative diseases. In ALS, mitochondrial dysfunction impairs the efficiency of electron transport chain (ETC) activity and ATP production and leads to the accumulation of reactive oxygen and nitrogen species, abnormal handling of intracellular calcium and cytochrome C release and apoptosis. The extent to which these alterations in mitochondrial functionimpair cellular operations is unclear. Therapeutic intervention based on combating these mitochondrial abnormalities have displayed variable success in mouse models of ALS and humans, as reviewed in Vandoorne et al.

Sean-Patrick Riechers, Jelena Mojsilovic-Petrovic, Tayler B. Belton, Ram P. Chakrabarty, ... Robert G. Kalb

Full text

 

Current Issue

Metformin overcomes metabolic reprogramming-induced resistance of skin squamous cell carcinoma to photodynamic therapy

Marta Mascaraque-Checa, María Gallego-Rentero, Jimena Nicolás-Morala, Mikel Portillo-Esnaola, ... Ángeles Juarranz

Objective

Cancer metabolic reprogramming promotes resistance to therapies. In this study, we addressed the role of the Warburg effect in the resistance to photodynamic therapy (PDT) in skin squamous cell carcinoma (sSCC). Furthermore, we assessed the effect of metformintreatment, an antidiabetic type II drug that modulates metabolism, as adjuvant to PDT.

Methods

For that, we have used two human SCC cell lines: SCC13 and A431, called parental (P) and from these cell lines we have generated the corresponding PDT resistant cells (10GT).

Results

Here, we show that 10GT cells induced metabolic reprogramming to an enhanced aerobic glycolysis and reduced activity of oxidative phosphorylation, which could influence the response to PDT. This result was also confirmed in P and 10GT SCC13 tumors developed in mice. The treatment with metformin caused a reduction in aerobic glycolysis and an increase in oxidative phosphorylation in 10GT sSCC cells. Finally, the combination of metformin with PDT improved the cytotoxic effects on P and 10GT cells. The combined treatment induced an increase in the protoporphyrin IX production, in the reactive oxygen species generation and in the AMPKexpression and produced the inhibition of AKT/mTOR pathway. The greater efficacy of combined treatments was also seen in vivo, in xenografts of P and 10GT SCC13 cells.

Conclusions

Altogether, our results reveal that PDT resistance implies, at least partially, a metabolic reprogramming towards aerobic glycolysis that is prevented by metformin treatment. Therefore, metformin may constitute an excellent adjuvant for PDT in sSCC.

Metformin overcomes metabolic reprogramming-induced resistance of skin squamous cell carcinoma to photodynamic therapy

Marta Mascaraque-Checa, María Gallego-Rentero, Jimena Nicolás-Morala, Mikel Portillo-Esnaola, ... Ángeles Juarranz

Objective

Cancer metabolic reprogramming promotes resistance to therapies. In this study, we addressed the role of the Warburg effect in the resistance to photodynamic therapy (PDT) in skin squamous cell carcinoma (sSCC). Furthermore, we assessed the effect of metformintreatment, an antidiabetic type II drug that modulates metabolism, as adjuvant to PDT.

Methods

For that, we have used two human SCC cell lines: SCC13 and A431, called parental (P) and from these cell lines we have generated the corresponding PDT resistant cells (10GT).

Results

Here, we show that 10GT cells induced metabolic reprogramming to an enhanced aerobic glycolysis and reduced activity of oxidative phosphorylation, which could influence the response to PDT. This result was also confirmed in P and 10GT SCC13 tumors developed in mice. The treatment with metformin caused a reduction in aerobic glycolysis and an increase in oxidative phosphorylation in 10GT sSCC cells. Finally, the combination of metformin with PDT improved the cytotoxic effects on P and 10GT cells. The combined treatment induced an increase in the protoporphyrin IX production, in the reactive oxygen species generation and in the AMPKexpression and produced the inhibition of AKT/mTOR pathway. The greater efficacy of combined treatments was also seen in vivo, in xenografts of P and 10GT SCC13 cells.

Conclusions

Altogether, our results reveal that PDT resistance implies, at least partially, a metabolic reprogramming towards aerobic glycolysis that is prevented by metformin treatment. Therefore, metformin may constitute an excellent adjuvant for PDT in sSCC.

2021 impact factor: 7.422

The 60 Second Metabolist

In this section authors briefly report on their work recently published in Molecular Metabolism.

Watch the most recent interviews by clicking the video still. 

Here is a video of Vimeo. When the iframes is activated, a connection to Vimeo is established and, if necessary, cookies from Vimeo are also used. For further information on cookies policy click here.

Here is a video of Vimeo. When the iframes is activated, a connection to Vimeo is established and, if necessary, cookies from Vimeo are also used. For further information on cookies policy click here.