Giant lysosomes as a chemotherapy resistance mechanism in hepatocellular carcinoma cells

Federico Colombo, Elena Trombetta, Paola Cetrangolo, Marco Maggioni, Paola Razini, Francesca De Santis, Yvan Torrente, Daniele Prati, Erminio Torresani, Laura Porretti

Research output: Contribution to journalArticle

Abstract

Despite continuous improvements in therapeutic protocols, cancer-related mortality is still one of the main problems facing public health. The main cause of treatment failure is multi-drug resistance (MDR: simultaneous insensitivity to different anticancer agents), the underlying molecular and biological mechanisms of which include the activity of ATP binding cassette (ABC) proteins and drug compartmentalisation in cell organelles. We investigated the expression of the main ABC proteins and the role of cytoplasmic vacuoles in the MDR of six hepatocellular carcinoma (HCC) cell lines, and confirmed the accumulation of the yellow anticancer drug sunitinib in giant (four lines) and small cytoplasmic vacuoles of lysosomal origin (two lines). ABC expression analyses showed that the main ABC protein harboured by all of the cell lines was PGP, whose expression was not limited to the cell membrane but was also found on lysosomes. MTT assays showed that the cell lines with giant lysosomes were more resistant to sorafenib treatment than those with small lysosomes (p

Original languageEnglish
Article numbere114787
JournalPLoS One
Volume9
Issue number12
DOIs
Publication statusPublished - Dec 10 2014

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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