title: Cytotoxic activities of hydroxyethyl piperazine-based σ receptor ligands on cancer cells alone and in combination with melphalan, PB28 and haloperidol.
abstract: σ Receptor ligands are attracting interest as possible anti-cancer agents because of their ability to induce cell death by different mechanisms. In this study we investigated the cytotoxic effects of 12 recently developed σ-receptor ligands in a panel of eight different human tumor cell lines by either the crystal violet or MTT assays. The results show that σ ligands have broad cytotoxic activity on a number of human cancer cell lines with IC50 values in the low μM range. In addition, apoptosis was observed by the annexin-V/PI double staining method when RPMI 8226 human multiple myeloma cells were treated with a representative σ ligand, (R)-2b. Combination of (R)-2b with melphalan led to a higher apoptotic rate than with the drug alone. Likewise, combined treatment of (R)-2b with the known high affinity σ2-agonist PB28 showed an additive effect on the induction of apoptosis in the RPMI 8226 line. In contrast, combinations of (R)-2b with the known σ1-antagonist haloperidol lead to a significant reduction in the cytotoxic activity of (R)-2b. These results support the idea that (R)-2b acts as a σ-agonist to cause the death of RPMI 8226 cells.
authors.forename: K
authors.initials: K
authors.lastname: Korpis
authors.forename: F
authors.initials: F
authors.lastname: Weber
authors.forename: B
authors.initials: B
authors.lastname: Wünsch
authors.forename: P J
authors.initials: PJ
authors.lastname: Bednarski
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D008558:Melphalan / Q000494:pharmacology*; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D017480:Receptors, sigma / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D014150:Antipsychotic Agents; C513937:PB28 compound; D010879:Piperazines; D017480:Receptors, sigma; D006220:Haloperidol; D008558:Melphalan