Primary effusion lymphoma (PEL) is a subtype of aggressive and chemotherapy-resistant non-Hodgkin lymphoma that occurs predominantly in patients with advanced AIDS. In this study, we examined the antitumor activity of methyl-beta-cyclodextrin (M-beta-CyD) in vitro and in vivo. M-beta-CyD quickly induced caspase-dependent apoptosis in PEL cells via cholesterol depletion from the plasma membrane. In a PEL xenograft mouse model, M-beta-CyD significantly inhibited the growth and invasion of PEL cells without apparent adverse effects. These results strongly suggest that M-beta-CyD has the potential to be an effective antitumor agent against PEL. (C) 2014 Elsevier Inc. All rights reserved.