Phenolic Compounds Isolated from Caesalpinia coriaria Induce S and G2/M Phase Cell Cycle Arrest Differentially and Trigger Cell Death by Interfering with Microtubule Dynamics in Cancer Cell Lines.

Jessica Sánchez-Carranza,Verónica Cuevas,Elizabeth Jiménez,Enrique Salas-Vidal,Laura Alvarez,Leticia González-Maya,Maelle Carraz,Silvia Marquina-Bahena,Rafael Veloz G

doi:10.3390/molecules22040666

Abstract

Caesalpinia coriaria (C. coriaria), also named cascalote, has been known traditionally in México for having cicatrizing and inflammatory properties. Phytochemical reports on Caesalpinia species have identified a high content of phenolic compounds and shown antineoplastic effects against cancer cells. The aim of this study was to isolate and identify the active compounds of a water:acetone:ethanol (WAE) extract of C. coriaria pods and characterize their cytotoxic effect and cell death induction in different cancer cell lines. The compounds isolated and identified by chromatography and spectroscopic analysis were stigmasterol, ethyl gallate and gallic acid. Cytotoxic assays on cancer cells showed different ranges of activities. A differential effect on cell cycle progression was observed by flow cytometry. In particular, ethyl gallate and tannic acid induced G2/M phase cell cycle arrest and showed interesting effect on microtubule stabilization in Hep3B cells observed by immunofluorescence. The induction of apoptosis was characterized by morphological characteristic changes, and was supported by increases in the ratio of Bax/Bcl-2 expression and activation of caspase 3/7. This work constitutes the first phytochemical and cytotoxic study of C. coriaria and showed the action of its phenolic constituents on cell cycle, cell death and microtubules organization.

Highlights

Cancer can be defined as the abnormal uncontrolled proliferation of cells in the body with the ability to invade and damage other surrounding tissues
The WAE extract of the pods of C. coriaria was assayed to determine its antiproliferative activity against PC3, Hep3B, and HepG2, Ca Ski and HeLa human cancer cell lines, as well as the immortalized human hepatocytes cell line IHH as control
IC50 were calculated, and the results showed that hepatocellular carcinoma HepG2 (16.5 μg/mL) and

Summary

Introduction

Cancer can be defined as the abnormal uncontrolled proliferation of cells in the body with the ability to invade and damage other surrounding tissues. Worldwide it is one of the main causes of death [1]. There is a growing awareness that the lower incidence of cancer in certain populations may be due to the consumption of certain nutrients, especially diets rich in polyphenols. It has been demonstrated that dietary polyphenols possess cancer preventive and therapeutic activities [2,3]. Polyphenolic compounds may promote apoptosis in cancer cells, modulating key elements in signal transduction pathways linked to apoptosis [4]

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