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Leuk Lymphoma. 2014 Mar;55(3):652-61. doi: 10.3109/10428194.2013.807927. Epub 2013 Jul 1.

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

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Department of Cancer Biology.


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.

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