Antileukemic Activity and Molecular Docking Study of a Polyphenolic Extract from Coriander Seeds.

Hamza Mechchate,Andrii Kyrylchuk,Regiane Costa De Oliveira,Gemilson Soares Pontes,Dalila Bousta,Emmily Myrella Vasconcelos Mourão,Mohamed Bouhrim,Andriy Grafov,Imane Es-Safi

doi:10.3390/ph14080770

Abstract

Leukemia is a group of hematological neoplastic disorders linked to high mortality rates worldwide, but increasing resistance has led to the therapeutic failure of conventional chemotherapy. This study aimed to evaluate in vitro the antileukemic activity and potential mechanism of action of a polyphenolic extract obtained from the seeds of Coriandrum sativum L. (CSP). A methylthiazoletetrazolium assay was performed to assess the CSP cytotoxicity on chronic (K562) and acute (HL60) myeloid leukemia cell lines and on normal Vero cell line. CSP toxicity was also evaluated in vivo using the OECD 423 acute toxicity model on Swiss albino mice. The results demonstrated a remarkable antitumoral activity against K562 and HL60 cell lines (IC50 = 16.86 µM and 11.75 µM, respectively) although no cytotoxicity was observed for the Vero cells or mice. A silico study was performed on the following receptors that are highly implicated in the development of leukemia: ABL kinase, ABL1, BCL2, and FLT3. The molecular docking demonstrated a high affinity interaction between the principal CSP components and the receptors. Our findings demonstrated that CSP extract has remarkable antileukemic activity, which is mainly mediated by the flavonoids, catechins, and rutin, all of which showed the highest binding affinity for the targeted receptors. This study revealed a promising active compound alternative research-oriented biopharmacists to explore.

Highlights

C. sativum seeds against two leukemia cell lines and a molecular docking study was performed
The LC/MS–MS revealed the presence of nine components which in the were determined calculating the area under the curve generated by the fragments comprepared extract: by vanillic acid, chlorogenic acid, catechin, epicatechin, epicatechin gallate, pared to that ofepigallocatechin, the standards and blanks, are provided in the gallocatechin, oleuropein, and rutin
The following commercial cell lines and reagents were used in the anticancer study: HL60 (ATCC ® CCL240TM-Human acute promyelocytic leukemia), K562 (ATCC® CCL243TM–chronic myelogenous leukemia), and Vero cells

Summary

Introduction

Leukemia is a heterogeneous group of hematological diseases characterized by the uncontrolled and dysfunctional growth of leukocytes [1]. Leukemia and nervous system cancers represent the primary causes of cancer mortality in men under the age of 40 and women under the age of 20 [2]. In 2020, approximately 60,530 new cases of leukemia were diagnosed, and 23,100 people are expected to die from this malignancy [2]. Human leukemia is caused by a combination of mutations that result in defects of gene expression, disrupting the fragile equilibrium of replication, differentiation, and apoptosis [3]. Cloning translocation breakpoints have given important insights into the pathogenesis of this disorder. Mutations in transcription factor genes involved in normal

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