Chrysophanol‐induced cell death (necrosis) in human lung cancer A549 cells is mediated through increasing reactive oxygen species and decreasing the level of mitochondrial membrane potential

Abstract

Chrysophanol (1,8-dihydroxy-3-methylanthraquinone) is one of the anthraquinone compounds, and it has been shown to induce cell death in different types of cancer cells. The effects of chrysophanol on human lung cancer cell death have not been well studied. The purpose of this study is to examine chrysophanol-induced cytotoxic effects and also to investigate such influences that involved apoptosis or necrosis in A549 human lung cancer cells in vitro. Our results indicated that chrysophanol decreased the viable A549 cells in a dose- and time-dependent manner. Chrysophanol also promoted the release of reactive oxygen species (ROS) and Ca(2+) and decreased the levels of mitochondria membrane potential (ΔΨm ) and adenosine triphosphate in A549 cells. Furthermore, chrysophanol triggered DNA damage by using Comet assay and DAPI staining. Importantly, chrysophanol only stimulated the cytocheome c release, but it did not activate other apoptosis-associated protein levels including caspase-3, caspase-8, Apaf-1, and AIF. In conclusion, human lung cancer A549 cells treated with chrysophanol exhibited a cellular pattern associated with necrotic cell death and not apoptosis in vitro. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 740-749, 2014.

Antitumor Effects of Chrysophanol in Malignant Optic Nerve Meningioma Cell Lines are Mediated via Caspase Activation, Induction of Mitochondrial Mediated Apoptosis, Mitochondrial Membrane Depolarization and Targeting the Mitogen-Activated Protein Kinase Signaling Pathway

“…It has been shown to trigger necrosis of the liver cancer cells by inducing the formation of ROS [10][11][12][13]. Similarly, in A549 lung cancer cells, chrysophanol causes the reduction of MMP loss to trigger cell death [11]. In yet another study, chrysophanol halted the ATP synthesis in liver cancer cells [12].…”

“…Previous studies have shown that chrysophanol inhibits the growth of cancer cells through different mechanisms [10]. It has been shown to trigger necrosis of the liver cancer cells by inducing the formation of ROS [10][11][12][13]. Similarly, in A549 lung cancer cells, chrysophanol causes the reduction of MMP loss to trigger cell death [11].…”

Bcl-2 Overexpression Inhibits Generation of Intracellular Reactive Oxygen Species and Blocks Adriamycin-induced Apoptosis in Bladder Cancer Cells

“…They are generated as by-products of electron transport through the mitochondrial respiratory chain as well as by γ-ray and ultraviolet light irradiations (Kaur et al, 2001). ROS are highly reactive toward intracellular macromolecules (DNA, proteins and lipids), causing severe lesions that can lead to the cell death by either necrosis or apoptosis, depending on the intensity of the oxidative stimuli (He et al, 2012;Ni et al, 2012;Plante et al, 2012).…”

Antitumor and Apoptotic Effects of Cucurbitacin a in a-549 Lung Carcinoma Cells Is Mediated via G2/M Cell Cycle Arrest and M-Tor/Pi3k/Akt Signalling Pathway.

“…Consistent with this, in China most cancer-related deaths are also due to lung cancer (Ni et al, 2014). In about 35-40% of patients, lung cancer advances to the metastatic stage with brain, bone and liver (Ferlay et al, 2010;Herbst et al, 2008).…”