Next Article in Journal
A Review of Cardiovascular Toxicity of Microcystins
Next Article in Special Issue
Investigation of the In-Vivo Cytotoxicity and the In Silico-Prediction of MDM2-p53 Inhibitor Potential of Euphorbia peplus Methanolic Extract in Rats
Previous Article in Journal
Baicalein Inhibits Stx1 and 2 of EHE: Effects of Baicalein on the Cytotoxicity, Production, and Secretion of Shiga Toxins of Enterohaemorrhagic Escherichia coli
Previous Article in Special Issue
Fusarubin and Anhydrofusarubin Isolated from A Cladosporium Species Inhibit Cell Growth in Human Cancer Cell Lines
Article

Annona cherimola Seed Extract Activates Extrinsic and Intrinsic Apoptotic Pathways in Leukemic Cells

1
Department of Natural Sciences, Lebanese American University, Beirut 13-5053, Lebanon
2
Laboratory of Regenerative Hematopoiesis, Swiss Institute for Experimental Cancer Research (ISREC) & Institute of Bioengineering (IBI), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
3
Department of Health Policy and Management, City University of New York, New York, NY 10027, USA
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(9), 506; https://doi.org/10.3390/toxins11090506
Received: 13 August 2019 / Revised: 28 August 2019 / Accepted: 28 August 2019 / Published: 30 August 2019
(This article belongs to the Collection Toxic and Pharmacological Effect of Plant Toxins)
Annona cherimola Mill is a large green fruit with black seeds widely known to possess toxic properties due to the presence of Annonaceous acetogenins. The present study investigates the anti-cancer properties of an Annona cherimola Mill ethanolic seed extract on Acute Myeloid Leukemia (AML) cell lines in vitro and elucidates the underlying cellular mechanism. The anti-proliferative effects of the extract on various AML cell lines and normal mesenchymal cells (MSCs) were assessed using WST-1 viability reagent. The pro-apoptotic effect of the extract was evaluated using Annexin V/PI staining and Cell Death ELISA. The underlying mechanism was deciphered by analyzing the expression of various proteins using western blots. Treatment with an A. cherimola seed ethanolic extract promotes a dose- and time-dependent inhibition of the proliferation of various AML cell lines, but not MSCs. Positive Annexin V staining, as well as DNA fragmentation, confirm an increase in apoptotic cell death by upregulating the expression of pro-apoptotic proteins which control both intrinsic and extrinsic pathways of apoptosis. GC/MS analysis revealed the presence of phytosterols, in addition to other bioactive compounds. In conclusion, Annona cherimola Mill seed extract, previously known to possess a potent toxic activity, induces apoptosis in AML cell lines by the activation of both the extrinsic and the intrinsic pathways. View Full-Text
Keywords: Annona cherimola Mill; apoptosis; cancer; leukemia; toxic Annona cherimola Mill; apoptosis; cancer; leukemia; toxic
Show Figures

Graphical abstract

MDPI and ACS Style

Haykal, T.; Nasr, P.; Hodroj, M.H.; Taleb, R.I.; Sarkis, R.; Moujabber, M.N.E.; Rizk, S. Annona cherimola Seed Extract Activates Extrinsic and Intrinsic Apoptotic Pathways in Leukemic Cells. Toxins 2019, 11, 506. https://doi.org/10.3390/toxins11090506

AMA Style

Haykal T, Nasr P, Hodroj MH, Taleb RI, Sarkis R, Moujabber MNE, Rizk S. Annona cherimola Seed Extract Activates Extrinsic and Intrinsic Apoptotic Pathways in Leukemic Cells. Toxins. 2019; 11(9):506. https://doi.org/10.3390/toxins11090506

Chicago/Turabian Style

Haykal, Tony, Peter Nasr, Mohammad H. Hodroj, Robin I. Taleb, Rita Sarkis, Marvy N.E. Moujabber, and Sandra Rizk. 2019. "Annona cherimola Seed Extract Activates Extrinsic and Intrinsic Apoptotic Pathways in Leukemic Cells" Toxins 11, no. 9: 506. https://doi.org/10.3390/toxins11090506

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop