The bisdioxopiperazine ICRF 187 is a potent intracellular chelating agent which effectively diminishes Adriamycin cardiotoxicity without compromising its antitumor activity. Our study aimed at verifying whether ICRF 187 can modulate the cytotoxic action of cisplatin (CDDP) on ovarian cancer cells. We used the A2780 ovarian cancer cell line and a subline resistant to CDDP (A2780-CDDP) obtained in our laboratory by continuous exposure of the parenatal cells to progressively increasing CDDP doses. In both cell lines ICRF 187 (0.1-0.5 microgram/ml) used in combination with CDDP (0.01-1 microgram/ml) produced a dose-dependent reduction of CDDP IC50 (the concentration inhibiting 50% of cell growth). Moreover, when ICRF 187 was used in combination with CDDP, analysis of the data by the isobole method showed that the combination of the two drugs produced a synergistic antiproliferative activity in both cell lines, with a CDDP potentiation up to fivefold. Our in vitro data show that ICRF 187 can synergize with CDDP. Prospective clinical trials are now needed to verify whether the addition of ICRF 187 to CDDP-containing regimens will result in an improved clinical response in ovarian cancer.

Bisdioxopiperazine, (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF 187), enhances the antiproliferative effect of cisplatin on human ovarian cancer cells / G., Scambia; BENEDETTI PANICI, Pierluigi; R. D., Bitta; P. B., Panici; R. D., Vincenzo; G., Contu; A., Ercoli; G., Bonanno; Pierelli, Luca; S., Mancuso. - In: GYNECOLOGIC ONCOLOGY. - ISSN 0090-8258. - 57:1(1995), pp. 16-22. [10.1006/gyno.1995.1094]

Bisdioxopiperazine, (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF 187), enhances the antiproliferative effect of cisplatin on human ovarian cancer cells.

BENEDETTI PANICI, PIERLUIGI;PIERELLI, LUCA;
1995

Abstract

The bisdioxopiperazine ICRF 187 is a potent intracellular chelating agent which effectively diminishes Adriamycin cardiotoxicity without compromising its antitumor activity. Our study aimed at verifying whether ICRF 187 can modulate the cytotoxic action of cisplatin (CDDP) on ovarian cancer cells. We used the A2780 ovarian cancer cell line and a subline resistant to CDDP (A2780-CDDP) obtained in our laboratory by continuous exposure of the parenatal cells to progressively increasing CDDP doses. In both cell lines ICRF 187 (0.1-0.5 microgram/ml) used in combination with CDDP (0.01-1 microgram/ml) produced a dose-dependent reduction of CDDP IC50 (the concentration inhibiting 50% of cell growth). Moreover, when ICRF 187 was used in combination with CDDP, analysis of the data by the isobole method showed that the combination of the two drugs produced a synergistic antiproliferative activity in both cell lines, with a CDDP potentiation up to fivefold. Our in vitro data show that ICRF 187 can synergize with CDDP. Prospective clinical trials are now needed to verify whether the addition of ICRF 187 to CDDP-containing regimens will result in an improved clinical response in ovarian cancer.
1995
dose-response relationship; drug synergism; antineoplastic agents; humans; drug effects; cell cycle; pharmacology/therapeutic use; cell division; female; drug therapy/pathology; ovarian neoplasms; tumor cells; cultured; razoxane; cisplatin; drug
01 Pubblicazione su rivista::01a Articolo in rivista
Bisdioxopiperazine, (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF 187), enhances the antiproliferative effect of cisplatin on human ovarian cancer cells / G., Scambia; BENEDETTI PANICI, Pierluigi; R. D., Bitta; P. B., Panici; R. D., Vincenzo; G., Contu; A., Ercoli; G., Bonanno; Pierelli, Luca; S., Mancuso. - In: GYNECOLOGIC ONCOLOGY. - ISSN 0090-8258. - 57:1(1995), pp. 16-22. [10.1006/gyno.1995.1094]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/399310
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