TY  - JOUR
AU  - Lopes-Rodrigues, Vanessa
AU  - Di Luca, Alessio
AU  - Mleczko, Justyna
AU  - Meleady, Paula
AU  - Henry, Michael
AU  - Pešić, Milica
AU  - Cabrera, Diana
AU  - van Liempd, Sebastiaan
AU  - Lima, Raquel T.
AU  - O’Connor, Robert
AU  - Falcon-Perez, Juan M.
AU  - Vasconcelos, M. Helena
PY  - 2017
UR  - http://www.nature.com/articles/srep44541
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2683
AB  - Multidrug resistance (MDR) is a serious obstacle to efficient cancer treatment. Overexpression of P-glycoprotein (P-gp) plays a significant role in MDR. Recent studies proved that targeting cellular metabolism could sensitize MDR cells. In addition, metabolic alterations could affect the extracellular vesicles (EVs) cargo and release. This study aimed to: i) identify metabolic alterations in P-gp overexpressing cells that could be involved in the development of MDR and, ii) identify a potential role for the EVs in the acquisition of the MDR. Two different pairs of MDR and their drug-sensitive counterpart cancer cell lines were used. Our results showed that MDR (P-gp overexpressing) cells have a different metabolic profile from their drug-sensitive counterparts, demonstrating decreases in the pentose phosphate pathway and oxidative phosphorylation rate; increases in glutathione metabolism and glycolysis; and alterations in the methionine/S-adenosylmethionine pathway. Remarkably, EVs from MDR cells were capable of stimulating a metabolic switch in the drug-sensitive cancer cells, towards a MDR phenotype. In conclusion, obtained results contribute to the growing knowledge about metabolic alterations in MDR cells and the role of EVs in the intercellular transfer of MDR. The specific metabolic alterations identified in this study may be further developed as targets for overcoming MDR.
T2  - Scientific Reports
T1  - Identification of the metabolic alterations associated with the multidrug resistant phenotype in cancer and their intercellular transfer mediated by extracellular vesicles
VL  - 7
DO  - 10.1038/srep44541
SP  - 44541
EP  - 44541
ER  - 

@article{
author = "Lopes-Rodrigues, Vanessa and Di Luca, Alessio and Mleczko, Justyna and Meleady, Paula and Henry, Michael and Pešić, Milica and Cabrera, Diana and van Liempd, Sebastiaan and Lima, Raquel T. and O’Connor, Robert and Falcon-Perez, Juan M. and Vasconcelos, M. Helena",
year = "2017",
abstract = "Multidrug resistance (MDR) is a serious obstacle to efficient cancer treatment. Overexpression of P-glycoprotein (P-gp) plays a significant role in MDR. Recent studies proved that targeting cellular metabolism could sensitize MDR cells. In addition, metabolic alterations could affect the extracellular vesicles (EVs) cargo and release. This study aimed to: i) identify metabolic alterations in P-gp overexpressing cells that could be involved in the development of MDR and, ii) identify a potential role for the EVs in the acquisition of the MDR. Two different pairs of MDR and their drug-sensitive counterpart cancer cell lines were used. Our results showed that MDR (P-gp overexpressing) cells have a different metabolic profile from their drug-sensitive counterparts, demonstrating decreases in the pentose phosphate pathway and oxidative phosphorylation rate; increases in glutathione metabolism and glycolysis; and alterations in the methionine/S-adenosylmethionine pathway. Remarkably, EVs from MDR cells were capable of stimulating a metabolic switch in the drug-sensitive cancer cells, towards a MDR phenotype. In conclusion, obtained results contribute to the growing knowledge about metabolic alterations in MDR cells and the role of EVs in the intercellular transfer of MDR. The specific metabolic alterations identified in this study may be further developed as targets for overcoming MDR.",
journal = "Scientific Reports",
title = "Identification of the metabolic alterations associated with the multidrug resistant phenotype in cancer and their intercellular transfer mediated by extracellular vesicles",
volume = "7",
doi = "10.1038/srep44541",
pages = "44541-44541"
}

Lopes-Rodrigues, V., Di Luca, A., Mleczko, J., Meleady, P., Henry, M., Pešić, M., Cabrera, D., van Liempd, S., Lima, R. T., O’Connor, R., Falcon-Perez, J. M.,& Vasconcelos, M. H.. (2017). Identification of the metabolic alterations associated with the multidrug resistant phenotype in cancer and their intercellular transfer mediated by extracellular vesicles. in Scientific Reports, 7, 44541-44541.
https://doi.org/10.1038/srep44541

Lopes-Rodrigues V, Di Luca A, Mleczko J, Meleady P, Henry M, Pešić M, Cabrera D, van Liempd S, Lima RT, O’Connor R, Falcon-Perez JM, Vasconcelos MH. Identification of the metabolic alterations associated with the multidrug resistant phenotype in cancer and their intercellular transfer mediated by extracellular vesicles. in Scientific Reports. 2017;7:44541-44541.
doi:10.1038/srep44541 .

Lopes-Rodrigues, Vanessa, Di Luca, Alessio, Mleczko, Justyna, Meleady, Paula, Henry, Michael, Pešić, Milica, Cabrera, Diana, van Liempd, Sebastiaan, Lima, Raquel T., O’Connor, Robert, Falcon-Perez, Juan M., Vasconcelos, M. Helena, "Identification of the metabolic alterations associated with the multidrug resistant phenotype in cancer and their intercellular transfer mediated by extracellular vesicles" in Scientific Reports, 7 (2017):44541-44541,
https://doi.org/10.1038/srep44541 . .

TY  - JOUR
AU  - Bizarro, Ana
AU  - Ferreira, Isabel C. F. R.
AU  - Soković, Marina
AU  - van Griensven, Leo J. L. D.
AU  - Sousa, Diana
AU  - Vasconcelos, M. Helena
AU  - Lima, Raquel T.
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1918
AB  - Cordyceps militaris (L.) Link, an edible entomopathogenic fungus widely
   used in traditional Chinese medicine, has numerous potential medicinal
   properties including antitumor activity. The methanolic extract of C.
   militaris fruiting body was recently shown to have tumor cell growth
   inhibitory activity in several human tumor cell lines. Nonetheless, the
   mechanism of action involved is still not known. This work aimed at
   further studying the effect of the methanolic extract of C. militaris
   regarding its antitumor mechanism of action, using the non-small cell
   lung cancer cell line (NCI-H460) as a model. Results showed that
   treatment with the extract decreased cellular proliferation, induced
   cell cycle arrest at G0/G1 and increased apoptosis. In addition, the
   extract increased the levels of p53 and p21. Moreover, an increase in
   p-H2A.X and 53BP1 levels, together with an increase in the number of
   53BP1 foci/cell (all indicative of DNA damage), were also observed after
   treatment with the extract. This work suggests that this extract
   affected NCI-H460 cellular viability through a mechanism involving DNA
   damage and p53 activation. This further supports the potential of this
   extract as a source of bioactive compounds, which may be used in
   anticancer strategies.
T2  - Molecules
T1  - Cordyceps militaris (L.) Link Fruiting Body Reduces the Growth of a
 Non-Small Cell Lung Cancer Cell Line by Increasing Cellular Levels of
 p53 and p21
IS  - 8
VL  - 20
DO  - 10.3390/molecules200813927
SP  - 13927
EP  - 13940
ER  - 

@article{
author = "Bizarro, Ana and Ferreira, Isabel C. F. R. and Soković, Marina and van Griensven, Leo J. L. D. and Sousa, Diana and Vasconcelos, M. Helena and Lima, Raquel T.",
year = "2015",
abstract = "Cordyceps militaris (L.) Link, an edible entomopathogenic fungus widely
   used in traditional Chinese medicine, has numerous potential medicinal
   properties including antitumor activity. The methanolic extract of C.
   militaris fruiting body was recently shown to have tumor cell growth
   inhibitory activity in several human tumor cell lines. Nonetheless, the
   mechanism of action involved is still not known. This work aimed at
   further studying the effect of the methanolic extract of C. militaris
   regarding its antitumor mechanism of action, using the non-small cell
   lung cancer cell line (NCI-H460) as a model. Results showed that
   treatment with the extract decreased cellular proliferation, induced
   cell cycle arrest at G0/G1 and increased apoptosis. In addition, the
   extract increased the levels of p53 and p21. Moreover, an increase in
   p-H2A.X and 53BP1 levels, together with an increase in the number of
   53BP1 foci/cell (all indicative of DNA damage), were also observed after
   treatment with the extract. This work suggests that this extract
   affected NCI-H460 cellular viability through a mechanism involving DNA
   damage and p53 activation. This further supports the potential of this
   extract as a source of bioactive compounds, which may be used in
   anticancer strategies.",
journal = "Molecules",
title = "Cordyceps militaris (L.) Link Fruiting Body Reduces the Growth of a
 Non-Small Cell Lung Cancer Cell Line by Increasing Cellular Levels of
 p53 and p21",
number = "8",
volume = "20",
doi = "10.3390/molecules200813927",
pages = "13927-13940"
}

Bizarro, A., Ferreira, I. C. F. R., Soković, M., van Griensven, L. J. L. D., Sousa, D., Vasconcelos, M. H.,& Lima, R. T.. (2015). Cordyceps militaris (L.) Link Fruiting Body Reduces the Growth of a
 Non-Small Cell Lung Cancer Cell Line by Increasing Cellular Levels of
 p53 and p21. in Molecules, 20(8), 13927-13940.
https://doi.org/10.3390/molecules200813927

Bizarro A, Ferreira ICFR, Soković M, van Griensven LJLD, Sousa D, Vasconcelos MH, Lima RT. Cordyceps militaris (L.) Link Fruiting Body Reduces the Growth of a
 Non-Small Cell Lung Cancer Cell Line by Increasing Cellular Levels of
 p53 and p21. in Molecules. 2015;20(8):13927-13940.
doi:10.3390/molecules200813927 .

Bizarro, Ana, Ferreira, Isabel C. F. R., Soković, Marina, van Griensven, Leo J. L. D., Sousa, Diana, Vasconcelos, M. Helena, Lima, Raquel T., "Cordyceps militaris (L.) Link Fruiting Body Reduces the Growth of a
 Non-Small Cell Lung Cancer Cell Line by Increasing Cellular Levels of
 p53 and p21" in Molecules, 20, no. 8 (2015):13927-13940,
https://doi.org/10.3390/molecules200813927 . .