0000000000593771
AUTHOR
N D'alessandro
Induction of apoptosis by arachidonic acid in human retinoblastoma Y79 cells: involvement of oxidative stress
Arachidonic acid administration caused apoptosis in Y79 cells, as shown by typical morphological changes, phosphatidylserine externalization, chromatin condensation, processing and activation of caspase-3 and cleavage of the endogenous caspase substrate poly-(ADP-ribose)-polymerase. Arachidonic acid also caused lamin B cleavage, suggesting caspase-6 activation. Arachidonic acid treatment was accompanied by increased formation of the lipid peroxidation end products malondialdehyde and 4-hydroxy-2-nonenal, lowering in reduced glutathione content and in mitochondrial membrane potential. Inhibiting glutathione synthesis sensitized Y79 cells to apoptosis-inducing stimuli, whilst replenishing red…
Antiproliferative and chemomodulatory effects of interferon-γ on doxorubicin-sensitive and -resistant tumor cell lines
Biological agents might offer various therapeutic opportunities in the treatment of cancer, including a direct and/or host-mediated antiproliferative effect and also the possibility to favorably modulate tumor resistance to antineoplastic drugs. We studied the in vitro antiproliferative effects of interferon (IFN)-gamma on the mouse B16 melanoma and Friend erythroleukemia, and the human K562 erythroleukemia, as doxorubicin (DXR)-sensitive and -resistant (multidrug resistant) variants. These effects were marked in B16 melanoma and rather slight in K562 erythroleukemia, without any difference between the DXR-sensitive and -resistant lines. The chemosensitive variant of Friend erythroleukemia …
Antioxidant defenses in a B16 melanoma line resistant to doxorubicin: an in vivo study.
A B16 melanoma line was repeatedly transplanted subcutaneously in C57BL/6 mice. On day 4 after every transplant, the animals were treated with doxorubicin (DXR), 10 mg/kg i.p. The aim of the work was to develop an in-vivo model of resistance to the antiblastic in order to analyze some possible mechanistic aspects of the process in the course of time. After 16 transplants and treatments the melanoma completely lost its sensitivity to the antiproliferative effects of maximal tolerated doses of DXR and showed over-expression of P-glycoprotein. Compared to the parental line, the in vitro resistance index was 4.6. After 27 transplants and treatments the melanoma did not increase its in vitro res…
Development and Partial Characterization of a Human T-Lymphoblastic Leukemic (CCRF-CEM) Cell Line Resistant to Etoposide. Analysis of Possible Circumventing Approaches
We have selected an etoposide-resistant variant (CCRF-CEM/VP-16) of the human T-lymphoblastic CCRF-CEM leukemia for study. Resistance to the topoisomerase II (topo II) inhibitor was about 11-fold and stable. Other data revealed that the new cell line had acquired an atypical, non-P-glycoprotein overexpressing multidrug resistant (MDR) phenotype with cross-resistance to other topo II inhibitors (amsacrine, doxorubicin, and mitoxantrone) and to glucocorticoids, but not to novobiocin, ICRF-187, vincristine or cisplatin. In a first instance, we assumed that altered drug-topo II interactions, based on quantitative and/or qualitative modifications of the enzyme, are a cause of resistance in the c…
Possible pharmacological interaction between corticosteroids and a calcineurin inhibitor (tacrolimus) in liver transplant patients.
Effects of Tumor Necrosis Factor-Alpha on Growth and Doxorubicin Sensitivity of Multidrug Resistant Tumor Cell Lines
Biological agents might offer various therapeutic opportunities in the treatment of cancer, including a direct and/or host- mediated antiproliferative effect as well as the possibility to favourably modulate tumor sensitivity to antineoplastic drugs (Alexander et al., 1987; Kikuchi et al., 1992; Wadler and Schwartz, 1990). However, information on their activity on chemoresistant tumors is still scanty (Billi et al., 1991; Bonavida et al., 1989; D’Alessandro, 1993; Fruehauf et al., 1991; Liddill et al., 1988; Mihich and Ehrke, 1991). Here we have focused on tumor necrosis-alpha (TNF-α) and studied its in vitro effects on the growth of two tumor cell lines, the mouse B16 melanoma and Friend e…
Effect of Buthionine Sulfoximine on the Sensitivity to Doxorubicin of Parent and MDR Tumor Cell Lines
We have studied the interaction of glutathione-depleting concentrations of buthionine sulfoximine (BSO) with the anti-proliferative activity of doxorubicin (DXR) in three tumor lines, the mouse B16 melanoma. Friend erythroleukemia and the human K562 leukemia, both as DXR-sensitive and-resistant (with typical multidrug resistance) variants. BSO significantly enhanced the DXR effects in the wild-type Friend and K562 leukemias, and especially in the drug-resistant subline of Friend leukemia. BSO did not modify DXR accumulation and retention in the latter clone. Moreover, neither BSO nor verapamil used alone completely reversed the resistance to DXR of this cell line; their combination was more…