Neem leaf extract induces cell death by apoptosis and autophagy in B-chronic lymphocytic leukemia cells

Abstract

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and is currently incurable. To expand the therapeutic armamentarium, we investigated neem leaf extract (NLE) after a patient with CLL demonstrated disease regression upon taking oral NLE. NLE-mediated apoptosis was examined in peripheral blood mononuclear cells (PBMCs) from 41 patients with CLL. NLE induced a dose-dependent reduction in CLL cell viability with significant apoptosis observed at 0.06% (w/v) by 24 h. Annexin-V staining and poly(ADP-ribose) polymerase 1 (PARP-1) and caspase 3 cleavage were observed after NLE treatment. However, a pan-caspase inhibitor only partially blocked NLE-mediated cell death. NLE also caused loss of mitochondrial outer membrane permeability and nuclear translocation of apoptosis-inducing factor. Furthermore, NLE treatment resulted in LC3-I cleavage. Biochemical analyses revealed that NLE also inhibits Bcl-2 and p53 proteins. In summary, NLE exhibits anti-leukemic properties in patient primary CLL cells and demonstrates clinical efficacy, warranting further investigation as a potential therapy for CLL.

Keywords::

• NLE
• CLL
• neem
• Azadirachta indica

Acknowledgements

The authors thank Dr. Kiersten Marie Miles for her technical help and Alison Dowdell for editing and formatting help.

Potential conflict of interest:

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

This work was supported in part by the Leukemia and Lymphoma Society (A.C.K. is a Leukemia and Lymphoma Society Scholar in Clinical Research).