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

Biomolecules. 2020 Jan 21;10(2):165. 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 -amylase enzyme and glucose uptake by yeast cells. The percentage glucose uptake and -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.

Keywords: Nyctanthes abor-tristis; acute myeloid leukemia; chronic lymphocytic leukemia; gas chromatography/mass spectrometry; human breast carcinoma; hypoglycemia; molecular docking; obesity; primary peripheral blood mononuclear cells; survivin protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology*
  • Alkenes / chemistry
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Proliferation
  • Drug Evaluation, Preclinical
  • Flowers / chemistry*
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Inhibitory Concentration 50
  • Jurkat Cells
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism*
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / metabolism*
  • Leukocytes, Mononuclear / cytology
  • MCF-7 Cells
  • Mice
  • Molecular Docking Simulation
  • Obesity / drug therapy
  • Oleaceae / chemistry*
  • Plant Extracts / pharmacology
  • Survivin / metabolism*

Substances

  • Alkenes
  • Antineoplastic Agents, Phytogenic
  • BIRC5 protein, human
  • Birc5 protein, mouse
  • Plant Extracts
  • Survivin
  • 1-octadecene