Curcumin nanodisk-induced apoptosis in mantle cell lymphoma

Abstract

Mantle cell lymphoma (MCL) is a pre-germinal center neoplasm characterized by cyclin D1 overexpression resulting from t(11;14)(q13;q32). Since MCL is incurable with standard lymphoma therapies, new treatment approaches are needed that target specific biologic pathways. In the present study, we investigated a novel drug delivery nanovehicle enriched with the bioactive polyphenol, curcumin (curcumin nanodisks; curcumin-ND). Cells treated with curcumin-ND showed a dose-dependent increase in apoptosis. This was accompanied by enhanced generation of reactive oxygen species (ROS). The antioxidant, N-acetylcysteine, inhibited curcumin-ND induced apoptosis, suggesting that ROS generation plays a role in curcumin action on MCL cells. Curcumin-ND decreased cyclin D1, pAkt, pIκBα, and Bcl₂ protein. In addition, enhanced FoxO3a and p27 expression as well as caspase-9, -3, and poly(ADP-ribose) polymerase (PARP) cleavage were observed. Curcumin-ND treatment led to enhanced G₁ arrest in two cultured cell models of MCL.

Keywords:

• Nanodisks
• mantle cell lymphoma
• curcumin
• cell cycle
• apoptosis

Acknowledgements

This study is supported by grants from The Northwestern University Feinberg School of Medicine Department of Medicine Lymphoma Research Fund (L.I.G.), the Meyer Research Fund (L.I.G.), and the Philip Bligh Research Fund (L.I.G.). The work was also supported by National Institutes of Health (NIH) grant HL-64159 (R.O.R.) from the National Heart, Lung and Blood Institute and the NIH Small Business Initiative Research award 1R43CA141904 (T.M.F.) from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. M.G. was supported by an American Heart Association Western States Affiliate Predoctoral Fellowship (#10PRE3600031).

The authors gratefully thank Dr. Steven H. Bernstein (University of Rochester, NY) for Granta and NCEB cells; and Dr. Steven Rosen (Northwestern University, Chicago, IL) for Jeko cells.

Potential conflict of interest:

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.