Enhancing effect of ATP on intracellular adriamycin penetration in human ovarian cancer cell lines

Ron Maymon, Batia Bar-Shira Maymon, Malca Cohen-Armon, Michael Holtzinger, Judith Leibovici

Research output: Contribution to journalArticlepeer-review

Abstract

Ovarian cancer has the highest mortality rate of all gynecological malignancies probably due to the evolution of clones resistant to cytotoxic drugs. Exploring possibilities to overcome such resistance constitutes a challenge in this study. We present the effect of adenosine triphosphate (ATP), serving a as chemosensitizerm, in combination with adriamycin on three human ovarian cancer cell lines of epithelial origin, OC-109, OC-238 and OC-7-NU, obtained from malignant ascites of different patients, and were proven to be tumorigenic in nude mice. The three lines differ in their sensitivity to the ATP-induced increase in adriamycin accumulation. FACS analysis showed a pronounced increase in intracellular adriamycin accumulation after treatment with various concentrations of ATP. In the OC-238 line, a 50.1% increase was observed at a low ATP concentration (200 μM), whereas higher concentrations (400 μM) and 500 μM) were needed to obtain an increase in ADR accumulation of 30% with the other two lines. Our study demonstrates that ATP improves the penetration of adriamycin at the neoplastic cellular level. Furthermore, our results may indicate that intratumoral ATP may serve as an alternative chemosensitizer which lacks the deleterious side effects of other chemosensitizing options.

Original languageEnglish
Pages (from-to)173-178
Number of pages6
JournalBiochimica et Biophysica Acta - General Subjects
Volume1201
Issue number2
DOIs
StatePublished - 11 Nov 1994

Keywords

  • (Ovarian carcinoma)
  • Adenosine triphosphate
  • Adriamycin
  • Chemosensitizing effect
  • Flow cytometry

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