Energy metabolism of human LoVo colon carcinoma cells: Correlation to drug resistance and influence of lonidamine

Maurizio Fanciulli, Tiziana Bruno, Aldo Giovannelli, Francesco P. Gentile, Monica Di Padova, Oriana Rubiu, Aristide Floridi

Research output: Contribution to journalArticle

Abstract

The relationship between modification of energy metabolism and extent of drug resistance was investigated in two sublines (LoVoDX and LoVoDX10) from human LoVo colon carcinoma cells that exhibit different degrees of resistance to doxorubicin. Results indicated that the extent of alteration in energy metabolism strictly correlated with degree of resistance. In LoVoDX cells, only 14CO2 production was enhanced, whereas in the more resistant LoVoDX10 cells, both 14CO2 and aerobic lactate production were stimulated. The basal and glucose-supported efflux rate and the amount of drug extruded by LoVoDX10 cells were significantly higher than in the resistant LoVoDX cells. Because the expression of surface P-170 glycoprotein was similar in both cell lines, this phenomenon was attributed to increased efflux pump activity resulting from greater ATP availability. Inhibition of 14CO2 production, aerobic glycolysis, and clonogenic activity by lonidamine (LND) increased with enhancement of the energy metabolism. Moreover, LND, by affecting energy-yielding processes, reduced intracellular ATP content, lowered the energy supply to the ATP-driven efflux pump, and inhibited, almost completely, doxorubicin extrusion by resistant LoVo cells. These findings strongly suggest that LND, currently used in tumor therapy, reduces drug resistance by restoring the capacity to accumulate and retain drug of cells with the MDR phenotype that overexpress P-170.

Original languageEnglish
Pages (from-to)1590-1597
Number of pages8
JournalClinical Cancer Research
Volume6
Issue number4
Publication statusPublished - Apr 2000

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Energy metabolism of human LoVo colon carcinoma cells: Correlation to drug resistance and influence of lonidamine'. Together they form a unique fingerprint.

  • Cite this

    Fanciulli, M., Bruno, T., Giovannelli, A., Gentile, F. P., Di Padova, M., Rubiu, O., & Floridi, A. (2000). Energy metabolism of human LoVo colon carcinoma cells: Correlation to drug resistance and influence of lonidamine. Clinical Cancer Research, 6(4), 1590-1597.