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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Administration, Oral
-
Antineoplastic Agents, Phytogenic / administration & dosage
-
Antineoplastic Agents, Phytogenic / pharmacology*
-
Antineoplastic Agents, Phytogenic / therapeutic use
-
Apoptosis / drug effects*
-
Apoptosis Inducing Factor / metabolism
-
Autophagy / drug effects*
-
Azadirachta / chemistry*
-
Cell Nucleus
-
Humans
-
Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
-
Leukemia, Lymphocytic, Chronic, B-Cell / metabolism*
-
Leukemia, Lymphocytic, Chronic, B-Cell / pathology
-
Leukocytes, Mononuclear / drug effects
-
Leukocytes, Mononuclear / metabolism
-
Membrane Potential, Mitochondrial / drug effects
-
Microtubule-Associated Proteins / metabolism
-
Neoplasm Staging
-
Plant Extracts / administration & dosage
-
Plant Extracts / pharmacology*
-
Plant Extracts / therapeutic use
-
Plant Leaves / chemistry*
-
Protein Transport / drug effects
-
Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
-
Reactive Oxygen Species / metabolism
-
Signal Transduction / drug effects
-
Tumor Cells, Cultured
-
Tumor Suppressor Protein p53 / antagonists & inhibitors
Substances
-
Antineoplastic Agents, Phytogenic
-
Apoptosis Inducing Factor
-
Microtubule-Associated Proteins
-
Plant Extracts
-
Proto-Oncogene Proteins c-bcl-2
-
Reactive Oxygen Species
-
Tumor Suppressor Protein p53