Therapeutic Efficacy of Nyctanthes arbor-tristis Flowers to Inhibit Proliferation of Acute and Chronic Primary Human Leukemia Cells, with Adipocyte Differentiation and in Silico Analysis of Interactions between Survivin Protein and Selected Secondary Metabolites

Saumya Nishanga Heendeniya,Lakshika Rangi Keerthirathna,Indeewarie Hemamali Dissanayake,Mohamed Boudjelal,Chamalika Kanthini Manawadu,Hajar Alzahrani,Dinithi Champika Peiris,Abdullah Mashhour,Rizwan Ali,Pahan Godakumbura

doi:10.3390/biom10020165

Abstract

Although the antidiabetic efficacy of Nyctanthes arbor-tristis flowers has been reported, antiproliferative and anti-obesity activities are yet to be explored. We examined the anti-obesity and antiproliferative potentials of different fractions (hexane, chloroform, ethyl acetate, methanol) of N. abor-tristis flower extract for the first time using 3T3-L1 cells, primary peripheral blood mononuclear cells (PBMC) isolated from healthy and adult acute myeloid (AML) and chronic lymphocytic leukemia (CLL) patients, recombinant Jurkat T cells, and MCF7 cell lines. The in vitro hypoglycemic activity was evaluated using the inhibition of α-amylase enzyme and glucose uptake by yeast cells. The percentage glucose uptake and α-amylase inhibitory activity increased in a dose-dependent manner in the crude and the tested fractions (hexane and ethyl acetate). Inhibition of the 3T3-L1 cells’ differentiation was observed in the ethyl acetate and chloroform fractions, followed by the hexane fraction. Antiproliferative analyses revealed that Nyctanthes exerted a high specific activity against anti-AML and anti-CLL PBMC cells, especially by the hexane and ethyl acetate fractions. The gas chromatography/mass spectrometry analysis indicated the presence of 1-heptacosanol (hexane fraction), 1-octadecene (hexane and chloroform fractions), and other organic compounds. Molecular docking demonstrated that phenol,2,5-bis(1,1-dimethylethyl) and 4-hydroxypyridine 1-oxide compounds showed specificity toward survivin protein, indicating the feasibility of N. abor-tristis in developing new drug leads against leukemia.

Highlights

In the 21st century, noncommunicable diseases, such as cancer, have been categorized as one of the most prominent barriers to increasing life expectancy [1]
Countries occupying the continents of South America, Africa, and Asia have been observed as having increased incidences of breast cancer, which is being related to factors ranging from genetics to a combination of demographic, social, and economic factors [2]
Scientific investigation has confirmed a possible link between cancer, diabetes, and obesity [48,49]

Summary

Introduction

In the 21st century, noncommunicable diseases, such as cancer, have been categorized as one of the most prominent barriers to increasing life expectancy [1]. Leukemia occurs mainly as a result of the abnormal multiplication of white blood cells and their precursors [4]. Leukemia can be divided into acute and chronic forms, where in acute leukemia, the abnormal blood cells remain immature and fail to carry normal functions. Depending on affected blood cells, leukemia can be categorized into lymphoblastic and myeloid leukemias. With lymphoblastic and myeloid leukemias, the malignant changes occur respectively in precursor cells of lymphocytes and red blood cells, and other white blood cell types and platelets. The acute myeloid leukemia is considered as the most common type on the basis of its highest incidences in both new cases and deaths in leukemia [8]

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Results

Conclusion