Enhanced cell death through combination of low doses of melphalan with nutlin-3. (A) Survival of NCI-H929 cells after a 5-day exposure to 1 μM melphalan (▦), 3-day exposure (days 3-5) to 2.5 μM nutlin-3a (), and a combination of both drugs (▨), relative to DMSO control (□). Combined treatment significantly reduced viability compared to any single-drug exposure. Western analysis showed that the level of p53 in NCI-H929 cells treated with both drugs was much higher than in cells exposed to either drug alone. (B) A combined low dose of melphalan (2 μM) and nutlin-3a (4 μM) showed increased antitumor activity in primary MM samples cocultured with BMSCs. MM cells were exposed to both drugs for 5 days.