PSC 833 modulation of multidrug resistance to paclitaxel in cultured human ovarian carcinoma cells leads to apoptosis.

Background: Multidrug resistance (MDR) modulator PSC 833 has been shown to modulate multidrug resistance in Pg-p-positive human ovarian carcinoma cells A2780/ADR. Co-treatment of A2780/ADR cells with paclitaxel (PTX) and PSC 833 resulted in the restoration of PTX-sensitivity comparable to that in parental A2780 cells.

Results: The flow cytometry experiments presented here showed PTX-(A2780) and PTX plus PSC 833 (A2780/ADR)-induced cell accumulation in the G2/M-phase of the cell cycle with concomitant appearance of apoptotic cells with sub-G0 (hypodiploid) DNA content.

PK11195, an isoquinoline carboxamide ligand of the mitochondrial benzodiazepine receptor, increased drug uptake and facilitated drug-induced apoptosis in human multidrug-resistant leukemia cells in vitro.

The isoquinoline peripheral benzodiazepine receptor ligand PK11195 increased drug (daunomycin)- and fluorochrome (calcein-AM) uptake and induced apoptosis detected by flow cytometry (FCM) technique, DNA electrophoretic analysis and poly(ADP-ribose) polymerase (PARP) cleavage in human multidrug-resistant myeloid leukemia (BL-60/VCR) and ovarian carcinoma (A2780/ADR) cells in vitro. The position of PK11195 with respect to drug-resistance modulator (DRM) efficiency, compared to the reference DRMs with the aid of FCM technique, was as follows: PSC833 > verapamil > PK11195 > vincristine. Our data show up to now not indicated observation that PK11195 possesses multidrug resistance modulating activity.

Non-steroidal anti-inflammatory agent ibuprofen-induced apoptosis, cell necrosis and cell cycle alterations in human leukemic cells in vitro.

The cytotoxic activity of the non-steroidal anti-inflammatory agent ibuprofen to human promyelocytic leukemia cell line HL-60, its multidrug-resistant subline HL-60/VCR (MDR-1 gene coded P-glycoprotein), as well as myeloma U266 and B-lymphoblastoid ARH-77 cell lines was demonstrated with the aid of flow cytometric analysis. Ibuprofen inhibited proliferation and induced apoptosis (detected as sub-G0 nuclei, fluorescein diacetate staining, Annexin-V binding cells and agarose electrophoretic detection of nucleosomal DNA fragmentation) in promyelocytic cells and, to a lesser extent, in U266 and ARH-77 cells.

Radiation-induced DNA damage and repair evaluated with 'comet assay' in human ovarian carcinoma cell lines with different radiosensitivities.

Radiation-induced DNA damage and kinetics of DNA repair was evaluated in three human ovarian carcinoma cell lines (i.e. CH-1, A-2780 and SKOV-3) with different sensitivities to ionizing radiation and radiation-induced apoptosis with the aid of single cell gel electrophoresis (SCGE, the comet assay).

PSC 833 induces apoptosis in drug-sensitive human leukemia cell line and modulates resistance to paclitaxel in its multidrug-resistant variant.

Background: The non-immunosuppressive cyclosporine analog PSC 833 has been shown to reverse multidrug-resistance of neoplastic cells including the MDR-1 gene coded P-glycoprotein (P-gp)-mediated cells resistant to paclitaxel.

Materials And Methods: Apoptosis was demonstrated in drug-sensitive HL-60 and multidrug-resistant human promyelocytic leukemia HL-60/ADR (MRP) and HL-60/VCR (MDR-1) cells in vitro with the aid of flow cytometry, DNA analysis and western blotting.

Results: The techniques used herein determined accumulation of paclitaxel/PSC 833 induced apoptotic cells with sub-G0 (hypodiploid) DNA content and blocked in the G2/M phase of the cell cycle, internucleosomal DNA fragmentation, poly (ADP-ribose) polymerase cleavage, Bcl-2 modulation and Bax up-regulation, without any significant alterations in the levels of Bcl-xL, CD95/Fas or Fas-L proteins.