1. A, chemical structures of PRIMA-1 and PRIMA-1Met.
A, chemical structures of PRIMA-1 and PRIMA-1Met. B–E, PRIMA-1Met displays preferential cytotoxic response to multiple myeloma cells of different p53 status. Multiple myeloma cells were plated in 96-well plates and cultured either with DMSO or different concentrations of PRIMA-1Met (2.5–40 μmol/L). After 48 hours, cell viability was assessed by MTT assay. Viability of the cells was expressed as percentage of the DMSO-treated control. Results represent the mean ± SD of three independent experiments done in triplicate. B, MM.1S, H929–harboring wild-type p53; C, LP1, U266, 8266–harboring mutant p53 and 8266R5 with null p53; D, primary multiple myeloma samples obtained from 9 newly diagnosed patients; three of nine samples carried hemizygous p53 deletion; E, PBMCs and BMMNCs. F, MM.1S, H929, U226, 8266, and 8226R5 cells were treated with different concentrations of PRIMA-1Met for 48 hours. Apoptosis was measured by Annexin V/propidium iodide–binding assay by flow cytometry. Apoptotic cells were quantified after normalizing with DMSO-treated cells. Results represent the mean ± SD.
Manujendra N. Saha et al. Mol Cancer Ther 2013;12:
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