title: 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.
authors.affiliation: Department of Cancer Biology.
authors.forename: Kasyapa S
authors.initials: KS
authors.lastname: Chitta
authors.forename: A Nazmul H
authors.initials: AN
authors.lastname: Khan
authors.forename: Noreen
authors.initials: N
authors.lastname: Ersing
authors.forename: Abhisek
authors.initials: A
authors.lastname: Swaika
authors.forename: Aisha
authors.initials: A
authors.lastname: Masood
authors.forename: Aneel
authors.initials: A
authors.lastname: Paulus
authors.forename: Abdul
authors.initials: A
authors.lastname: Qadeer
authors.forename: Pooja
authors.initials: P
authors.lastname: Advani
authors.forename: Taimur
authors.initials: T
authors.lastname: Sher
authors.forename: Kena C
authors.initials: KC
authors.lastname: Miller
authors.forename: Kelvin
authors.initials: K
authors.lastname: Lee
authors.forename: Asher A
authors.initials: AA
authors.lastname: Chanan-Khan
mesh_terms: D000284:Administration, Oral; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D031601:Azadirachta / Q000737:chemistry*; D002467:Cell Nucleus; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves / Q000737:chemistry*; D021381:Protein Transport / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051033:Apoptosis Inducing Factor; D008869:Microtubule-Associated Proteins; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53