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

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.

Advances in Azorella glabra Wedd. Extract Research: In Vitro Antioxidant Activity, Antiproliferative Effects on Acute Myeloid Leukemia Cells and Bioactive Compound Characterization

“…The activation of this pathway is one of the key mechanisms involved in the role of many antitumor drugs [ 58 ], so its identification provides indications for new possible target therapies. Our results are in accordance with other recent works reporting the activation of the pathway after treatment with different plant extracts [ 59 , 60 ]. Interestingly, we confirmed the increase of apoptosis after treatment with IV and VI also in primary cells of three AML patients with diverse mutational status ( Figure 7 ).…”

Nettle Tea Inhibits Growth of Acute Myeloid Leukemia Cells In Vitro by Promoting Apoptosis

“…Untreated cells were used as controls. Cells were collected and centrifuged after 48 and 72 h of treatment, and the pellets were stained with both annexin V and PI (annexin V-fluorescein isothiocyanate (FITC) Apoptosis Detection Kit, Abcam, Cambridge, UK) and immediately analyzed using the Accuri C6 flow cytometer, as previously described [26,27]. Upon apoptosis induction, phosphatidyl serine is translocated to the outer leaflet of the cell membrane, and living cells exclude PI from the cytoplasm.…”

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

“…Overall, triggering reactive oxygen species (ROS) production is a promising strategy in cancer therapy, since these reactive species are involved in stimulation of apoptosis through mitochondrial dysfucntion and much attention has been directed toward enhancing the ROS generation in cancer cells to suppress their malignancy and proliferation [66,67]. To date, there has been no article to investigate the relationship between the inhibitory effect of resveratrol on ROS production and its anti-tumor activity.…”