Influence of a cholesterol-rich emulsion and BCNU on the apoptotic indices of myeloma cells induced in BALB/C mice

ABSTRACT

Proliferating malignant cells express low-density lipoprotein (LDL) receptors, and a cholesterol-rich microemulsion (LDE) resembling the lipid portion of LDL can be bound to lipophilic drugs such as 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) to increase the drug´s capture and decrease the drug-associated toxicity. In this work, we studied the effect of BCNU and BCNU+LDE on apoptosis in plasmacytoma-related cells obtained from BALB/c mice with myeloma. Four groups of mice (n=4 each) were treated with LDE, BCNU, BCNU in LDE or vehicle solution (control group). Morphological methods (histology and transmission electron microscopy) and immunohistochemistry (TUNEL procedure) were used to evaluate the occurrence of apoptosis. The drugs were injected intraperitoneally in the 14th month after induction of the myeloma and the mice in all groups were sacrificed six hours after this injection. The apoptotic indices of the plasmacytoma mesenteric cells evaluated in the four experimental groups revealed that the LDE emulsion significantly (p<0.05) increased the percentage of tumoral cells dying by apoptosis. All the groups with LDE, alone or in combination with BCNU showed significantly higher apoptotic indices than the controls. This enhanced cytotoxicity suggests a potential use for LDE in improving the efficacy of chemotherapeutic agents.