title: Comparative evaluation of pirarubicin and adriamycin in gynecologic cancer cell lines.
abstract: Pirarubicin (PIRA) has been shown to have improved potency with less cardiac toxicity in several phase I and II clinical trials in Japan and Europe. Since Adriamycin (DXR) remains one of the most potent drugs in treatment of gynecologic cancers, this derivative has the potential to become an important chemotherapeutic agent. In this study, we compared the performance of these two drugs against a panel of 10 gynecologic cancer cell lines. The ATP chemosensitivity assays were used to determine dose-response curves. Flow cytometry was used to study cell kinetic response to both drugs. Using an IC50 value of 0.2 micrograms/ml as a cutoff for drug sensitivity, 4 cell lines, ECC1, HEC1B, BG1, and SKOV3, were considered resistant to DXR. By comparing IC50s, PIRA was 3.4 +/- 0.4 times more potent than DXR (P = 0.05). The other 6 cell lines, AN3, AE7, HEC1A, CAOV3, SKUT1B, and ME180, were considered sensitive to DXR. In this group of cell lines, PIRA was 1.6 +/- 0.3 times more potent than DXR (P = 0.5). Both PIRA and DXR elicited a spectrum of cell kinetics. By comparing the magnitude of G2 blocks at 0.1 micrograms/ml, PIRA was approximately 2-5 times more potent than DXR in SKUT1B, HEC1A, and BG1 cell lines. PIRA also displayed a reverse dose-response pattern of G2 block so that at high dose, cell cycle kinetics would mirror those of untreated controls. This observation supports the presence of a resistant tumor subpopulation and the concept of tumor heterogeneity.
authors.affiliation: Department of Obstetrics & Gynecology, University of Miami School of Medicine, Florida 33136.
authors.forename: H N
authors.initials: HN
authors.lastname: Nguyen
authors.forename: B U
authors.initials: BU
authors.lastname: Sevin
authors.forename: H
authors.initials: H
authors.lastname: Averette
authors.forename: J
authors.initials: J
authors.lastname: Perras
authors.forename: M
authors.initials: M
authors.lastname: Untch
authors.forename: R
authors.initials: R
authors.lastname: Ramos
authors.forename: D
authors.initials: D
authors.lastname: Donato
authors.forename: M
authors.initials: M
authors.lastname: Penalver
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007700:Kinetics; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; C027260:pirarubicin