Title:Flavonoid Kaempferol Inhibits the Proliferation and Survival of Human Leukemia HL60 Cells

VOLUME: 16 ISSUE: 4

Author(s):Saleheh Rezapour, Elham Hosseinzadeh, Afsaneh Jahangiryan, Behnam Emamgolizade Gurd Tapeh, Nasrin Beheshtkhoo, Mohammad Amin Jadidi Kouhbanani, Ali Hassanzadeh and Faroogh Marofi*

Affiliation:Department of Medical Genetic, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Department of Medical Genetic, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Immunology Department, Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine (IBTO), Tehran, Department of Immunology, Division of Hematology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Department of Immunology, Division of Hematology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Department of Immunology, Division of Hematology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz

Keywords:Kaempferol (Kae), acute myeloid leukemia (AML), proliferation, apoptosis, HL60 cells, real-time PCR.

Abstract:

Background: Acute myeloid leukemia (AML) is an aggressive type of leukemia adversely affecting the normal differentiation and proliferation process of human hematopoietic myeloid lineage. Over the last decades, Kaempferol (Kae) (3,4′,5,7-tetrahydroxyflavone) has been considered a flavonoid with useful medical significance, capable of inhibiting various types of leukemia (e.g., AML).

Objective: This study aimed to evaluate the Kae effect on proliferation and apoptosis of a human AML cell line, HL60.

Methods: The proliferation capability of the HL60 cells was estimated by MTT assay at 12, 24, and 48 hours after exposure to Kae at a series of concentrations, including 10, 25, 50, and 75 μM. Also, the apoptosis level of HL60 cells was measured 48 hours after exposure to various concentrations of Kae (10, 25, and 50 μM) using Annexin-V/PI staining and FACS analysis. Besides, the gene expression of CDK1/2, Bcl-2, survivin, c-FLIP, Mcl-1, XIAP, Bax, and caspase 3 and 8 was assessed following treatment of HL60 cells with Kae (25 and 50 μM) by Real-Time PCR.

Results: The anti-proliferation activity of Kae showed an ascending pattern over time and reached the maximum level at 48 hours of HL60 cells exposure to Kae. Also, it was able to trigger apoptosis of HL60 cells, in particular, at 50 μM concentration. On the other hand, Kae could modify the expression levels of the candidate’s genes in treated cells.

Conclusion: The promising results of using Kae against the HL60 cells have made it a good drug candidate to treat AML through up-regulation of caspases expression and down-regulation of antiapoptotic proteins.