Neoplastic cells accumulate magnesium, an event which provides selective advantages and is frequently associated with TRPM7overexpression. Little is known about magnesium homeostasis in drug-resistant cancer cells. Therefore, we used the colon cancer LoVo cell model and compared doxorubicin-resistant to sensitive cells. In resistant cells the concentration of total magnesium is higher while its influx capacity is lower than in sensitive cells. Accordingly, resistant cells express lower amounts of the TRPM6 and 7, both involved in magnesium transport. While decreased TRPM6 levels are due to transcriptional regulation, post-transcriptional events are involved in reducing the amounts of TRPM7. Indeed, the calpain inhibitor calpeptin markedly increases the levels of TRPM7 in resistant cells. In doxorubicin-sensitive cells, silencing TRPM7 shifts the phenotype to one more similar to resistant cells, since in these cells silencing TRPM7 significantly decreases the influx of magnesium, increases its intracellular concentration and increases resistance to doxorubicin. On the other hand, calpain inhibition upregulates TRPM7, decreases intracellular magnesium and enhances the sensitivity to doxorubicin of resistant LoVo cells. We conclude that in LoVo cells drug resistance is associated with alteration of magnesium homeostasis through modulation of TRPM7. Our data suggest that TRPM7 expression may be an additional undisclosed player in chemoresistance.

Castiglioni, S., Cazzaniga, A., Trapani, V., Cappadone, C., Farruggia, G., Merolle, L., Wolf, F., Iotti, S., Maier, J. A., Magnesium homeostasis in colon carcinoma LoVo cells sensitive or resistant to doxorubicin, <<SCIENTIFIC REPORTS>>, 2015; (5): 16538-16538. [doi:10.1038/srep16538] [http://hdl.handle.net/10807/71706]

Magnesium homeostasis in colon carcinoma LoVo cells sensitive or resistant to doxorubicin

Trapani, Valentina;Wolf, Federica;
2015

Abstract

Neoplastic cells accumulate magnesium, an event which provides selective advantages and is frequently associated with TRPM7overexpression. Little is known about magnesium homeostasis in drug-resistant cancer cells. Therefore, we used the colon cancer LoVo cell model and compared doxorubicin-resistant to sensitive cells. In resistant cells the concentration of total magnesium is higher while its influx capacity is lower than in sensitive cells. Accordingly, resistant cells express lower amounts of the TRPM6 and 7, both involved in magnesium transport. While decreased TRPM6 levels are due to transcriptional regulation, post-transcriptional events are involved in reducing the amounts of TRPM7. Indeed, the calpain inhibitor calpeptin markedly increases the levels of TRPM7 in resistant cells. In doxorubicin-sensitive cells, silencing TRPM7 shifts the phenotype to one more similar to resistant cells, since in these cells silencing TRPM7 significantly decreases the influx of magnesium, increases its intracellular concentration and increases resistance to doxorubicin. On the other hand, calpain inhibition upregulates TRPM7, decreases intracellular magnesium and enhances the sensitivity to doxorubicin of resistant LoVo cells. We conclude that in LoVo cells drug resistance is associated with alteration of magnesium homeostasis through modulation of TRPM7. Our data suggest that TRPM7 expression may be an additional undisclosed player in chemoresistance.
eng
Castiglioni, S., Cazzaniga, A., Trapani, V., Cappadone, C., Farruggia, G., Merolle, L., Wolf, F., Iotti, S., Maier, J. A., Magnesium homeostasis in colon carcinoma LoVo cells sensitive or resistant to doxorubicin, <>, 2015; (5): 16538-16538. [doi:10.1038/srep16538] [http://hdl.handle.net/10807/71706]
File in questo prodotto:
File Dimensione Formato  
71706oa.pdf

accesso aperto

Tipologia file ?: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 917.64 kB
Formato Adobe PDF
917.64 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/71706
Citazioni
  • ???jsp.display-item.citation.pmc??? 18
  • Scopus 33
  • ???jsp.display-item.citation.isi??? 35
social impact