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Abstract

Antitumor effect of cyclophosphamide on LS and P388 tumors is realized via apoptosis and on HA-1 and Krebs-2 tumors resistant to apoptosis via necrosis of tumor cells. Phenobarbital induction of cyclophosphamide-metabolizing enzymes decreases and cimetidine inhibition potentiates the effect of cyclophosphamide on LS and P388 cells and does not modulate the effect on HA-1 and Krebs-2 cells. Presumably, apoptosis and necrosis of tumor cell are induced by different cyclophosphamide metabolites.

Cyclophosphamide metabolite inducing apoptosis in RLS mouse lymphosarcoma cells is a substrate for P-glycoprotein

“…Thus, CP induced apoptotic death of RLS tumor cells, but in this case its dose was 10-fold higher than for LS tumor [3]. Elucidation of the mechanisms underlying the differences in CP doses triggering apoptosis in tumor cells was one of the tasks of our study.…”

“…1). We previously showed that CP in a dose of 25 mg/kg inhibits the growth of solid LS tumor and had no effect on the growth of solid RLS tumor [3]. Cytophotometry showed that after CP treatment the number of cells with haploid DNA content (indicator of apoptosis) in LS tumor increased by more than 6-times (from 4.5 to 27.8%), while in RLS tumor this parameter re mained at the control level (<3%) [1].…”

“…We previously obtained t ransplantable murine lymphosarcoma LS highly sensitive to the therapeutic effect of cyclophosphamide (CP) and its daughter strain RLS exhibiting resistance to low doses of cyclophosphamide [1][2][3]6]. Despite different sensitivity to apoptosis induction, these tumors did not differ by the expression of proapoptotic (bax and bad) and antiapoptotic (bcl-2 and bcl- 6) genes.…”

Development of a new generation of drug dosage forms by construction of liposomal nanocontainers

“…The freeze−thaw cycle is repeated six times. The mixture thawed after the last cycle is diluted with a 4-fold volume of a 0.14 М solution of NaCl to suspend large unilamellar liposomes [25].…”