TY - JOUR
T1 - Enhancing effect of ATP on intracellular adriamycin penetration in human ovarian cancer cell lines
AU - Maymon, Ron
AU - Bar-Shira Maymon, Batia
AU - Cohen-Armon, Malca
AU - Holtzinger, Michael
AU - Leibovici, Judith
N1 - Funding Information:
* Corresponding author. Fax: + 972 3 6409043. 1 In partial fulfillment towards a Postdoctoral Fellowship, supported by the Wolf Foundation to Promote Science and Art for the Benefit of Mankind.
PY - 1994/11/11
Y1 - 1994/11/11
N2 - 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.
AB - 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.
KW - (Ovarian carcinoma)
KW - Adenosine triphosphate
KW - Adriamycin
KW - Chemosensitizing effect
KW - Flow cytometry
UR - http://www.scopus.com/inward/record.url?scp=0027947441&partnerID=8YFLogxK
U2 - 10.1016/0304-4165(94)90038-8
DO - 10.1016/0304-4165(94)90038-8
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AN - SCOPUS:0027947441
SN - 0304-4165
VL - 1201
SP - 173
EP - 178
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 2
ER -
