['More than 50% of human breast cancers express receptors for luteinizing hormone-releasing hormone (LHRH-R). These receptors can be used for targeted chemotherapy with agents like AN-152, in which doxorubicin is linked to analog [D-Lys6]LHRH. We compared the effects of AN-152 and doxorubicin in human breast cancer cells.', 'MCF-7, T47D, HCC-70 and ZR-75-1 cells were analysed for expression of LHRH-R using RT-PCR, immunostaining and flow cytometry. Apoptosis and expression of MDR-1 gene product Pgp were measured by flow cytometry. Cleavage of doxorubicin from AN-152 by serum carboxylesterase (CE) was inhibited by DFP.', 'In MCF-7, T47D and HCC-70 cells we found cell surface expression of LHRH-R. In ZR-75-1 cells only sparse surface expression was found. In HCC-70 cells, induction of apoptosis by AN-152 was stronger than by doxorubicin in medium containing fetal calf serum (FCS). Pretreatment with DFP increased AN-152-induced apoptosis in LHRH-R positive MCF-7 and HCC-70 cells and reduced apoptosis in ZR-75-1 cells. In serum-free medium apoptosis induced by AN-152 was stronger than that induced by doxorubicin in HCC-70, T47D and MCF-7 cells, but weaker in ZR-75-1 cells. In medium containing FCS, both AN-152 and doxorubicin induced surface expression of MDR-1 gene product Pgp, but the effect of AN-152 was weaker. Pgp-expression induced by AN-152 was inhibited by pretreatment with DFP. AN-152 did not induce Pgp-expression in serum-free medium.'] Is induction of apoptosis by AN-152 , a cytotoxic analog of luteinizing hormone-releasing hormone ( LHRH ) , in LHRH-R positive human breast cancer cells independent of multidrug resistance-1 ( MDR-1 ) system?