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

Kasyapa S. Chitta, A. Nazmul H Khan, Noreen Ersing, Abhisek Swaika, Aisha Masood, Aneel Paulus, Abdul Qadeer, Pooja Advani, Taimur Sher, Kena C. Miller, Kelvin Lee, Asher A Chanan Khan

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)652-661
Number of pages10
JournalLeukemia and Lymphoma
Volume55
Issue number3
DOIs
StatePublished - Mar 2014

Fingerprint

Autophagy
B-Cell Chronic Lymphocytic Leukemia
Cell Death
Apoptosis
Apoptosis Inducing Factor
Caspase Inhibitors
Annexin A5
Mitochondrial Membranes
Therapeutics
Caspase 3
Permeability
Blood Cells
Cell Survival
Leukemia
Staining and Labeling
Proteins

Keywords

  • Azadirachta indica
  • CLL
  • Neem
  • NLE

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Neem leaf extract induces cell death by apoptosis and autophagy in B-chronic lymphocytic leukemia cells. / Chitta, Kasyapa S.; Khan, A. Nazmul H; Ersing, Noreen; Swaika, Abhisek; Masood, Aisha; Paulus, Aneel; Qadeer, Abdul; Advani, Pooja; Sher, Taimur; Miller, Kena C.; Lee, Kelvin; Chanan Khan, Asher A.

In: Leukemia and Lymphoma, Vol. 55, No. 3, 03.2014, p. 652-661.

Research output: Contribution to journalArticle

Chitta, KS, Khan, ANH, Ersing, N, Swaika, A, Masood, A, Paulus, A, Qadeer, A, Advani, P, Sher, T, Miller, KC, Lee, K & Chanan Khan, AA 2014, 'Neem leaf extract induces cell death by apoptosis and autophagy in B-chronic lymphocytic leukemia cells', Leukemia and Lymphoma, vol. 55, no. 3, pp. 652-661. https://doi.org/10.3109/10428194.2013.807927
Chitta, Kasyapa S. ; Khan, A. Nazmul H ; Ersing, Noreen ; Swaika, Abhisek ; Masood, Aisha ; Paulus, Aneel ; Qadeer, Abdul ; Advani, Pooja ; Sher, Taimur ; Miller, Kena C. ; Lee, Kelvin ; Chanan Khan, Asher A. / Neem leaf extract induces cell death by apoptosis and autophagy in B-chronic lymphocytic leukemia cells. In: Leukemia and Lymphoma. 2014 ; Vol. 55, No. 3. pp. 652-661.
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