Malva pseudolavatera Leaf Extract Promotes ROS Induction Leading to Apoptosis in Acute Myeloid Leukemia Cells In Vitro.

Marianne El Khoury,Tony Haykal,Rita Sarkis,Mohammad H Hodroj,Sandra Rizk,Sonia Abou Najem,Robin I Taleb

doi:10.3390/cancers12020435

Marianne El Khoury, Tony Haykal + Show 5 more

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https://doi.org/10.3390/cancers12020435

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Journal: Cancers	Publication Date: Feb 13, 2020
Citations: 20	License type: CC BY 4.0

Affiliation: Lebanese American University

Abstract

Malva pseudolavatera Webb & Berthel. is a plant from the Malvaceae family that has long been included in the human diet due to its various curative effects. Many plant leaf extracts from the various species of Malva genus have been reported to possess anti-cancer properties, however, studies on M. pseudolavatera Webb & Berthel. leaves have documented anti-inflammatory and anti-oxidant effects with no emphasis on their possible anti-cancer potential. The present study explores the anti-cancer properties of Malva pseudolavatera Webb & Berthel. leaf extract on acute myeloid leukemia (AML) cell lines in vitro and deciphers the underlying molecular mechanism. Treatment of AML cell lines with M. pseudolavatera methanolic leaf extract showed a dose- and time-dependent inhibition of proliferation and a dose-dependent increase in apoptotic hallmarks such as an increase in phosphatidylserine on the outer membrane leaflet and membrane leakage in addition to DNA fragmentation. The pro-apoptotic effect was induced by reactive oxygen species (ROS) as well as an upregulation of cleaved poly(ADP-ribose) polymerase (PARP), increase in Bax/Bcl-2 ratio, andrelease of cytochrome-c from the mitochondria. Major compounds of the extract included methyl linolenate, phytol, γ-sitosterol, and stigmasterol as revealed by gas chromatography coupled with mass spectrometry, and amino acids, amino acid derivatives, tiliroside, 13-hydroxyperoxyoctadecadienoic, and quercitrin as detected by liquid chromatography coupled to mass spectrometry.

Highlights

Malva pseudolavatera Webb & Berthel. is an annual or biennial subshrub that grows in fields and roadsides in coastal areas and low-altitude mountain regions [1]
We investigated the potential anti-cancer properties of M. pseudolavatera Webb & Berthel. methanolic leaf extract (MMLE) on acute myeloid leukemia (AML) cell lines in vitro and deciphered the underlying molecular mechanism
A dose-dependent and time-dependent significant decrease in proliferation of the three AML cell lines, Monomac-1, KG-1, and U937 was observed with an IC50 of 200 μg/mL and 86.80 μg/mL for Monomac-1 (Figure 1A), 207.9 μg/mL and 89.47 μg/mL for KG-1 (Figure 1B), and 402 μg/mL and 229 μg/mL for U937 (Figure 1C) after 24 h and 48 h, respectively

Summary

Introduction

Malva pseudolavatera Webb & Berthel. is an annual or biennial subshrub that grows in fields and roadsides in coastal areas and low-altitude mountain regions [1]. Known as “tree mallow” in North America and “khubbaza” in the Middle East, it is a plant of the Malvaceae family [2]. Named Lavatera cretica (Malvaceae family), the species was transferred to the Malva genus and is currently called M. pseudolavatera or Malva linnaei or Malva multiflora [3]. Apart from being used as food in some regions such as in Turkey, Spain, and Pakistan, leaves of the Malva genus plants have been traditionally used in folk medicine all around the world to treat a multitude of diseases, most commonly diarrhea, arthritis, inflammation, cough, and respiratory infections [5]. Among the 50 species of Malva, M. pseudolavatera Webb & Berthel. In Spain, it is considered as a remedy for influenza, upper respiratory tract infections, and cough [7], whereas in Portugal, it is used for its laxative, analgesic, and antiseptic effects [8]

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