Generation of Free Radicals by Emodic Acid and its [d-Lys6]GnRH-conjugate¶

Abstract

In an attempt to develop an efficient chemotherapeutic agent targeted at malignant cells that express receptors to gonadotropin releasing hormone (GnRH) we coupled [D-Lys 6 ]GnRH covalently to an emodin derivative, i.e. emodic acid (Emo) to yield [D-Lys 6 (Emo)]GnRH. Emodin is a naturally occurring anthraquinone which is widely used as a laxative and has other versatile biological activities. Physico-chemical studies employing electron paramagnetic resonance and electrochemistry of the conjugate as well as the (Emo) moiety showed that these compounds could be easily reduced either chemically, photochemically or enzymatically to their corresponding semiquinones. In the presence of oxygen the semiquinones generated reactive oxygen species (ROS), mainly superoxide and hydroxyl radicals, which were detected by the spin trapping method. Moreover, upon irradiation with visible light these compounds produced ROS and a highly reactive excited triplet state of Emo, which by itself may cause the oxidation of certain electron acceptors such as amino acids and bases of nucleic acids. Thus, [D-Lys 6 ]GnRH-photosensitizer conjugates may be potentially used for targeted photodynamic chemotherapy aimed at treating cancer cells that carry GnRH receptors. These conjugates may also induce cytotoxicity in the dark similar to common conventional chemotherapeutic agents. The peptidic moiety, [D-Lys 6 ]GnRH, was found to be stable toward highly reactive ROS generated either from enzymatic reduction or upon photoirradiation. The physico-chemical properties of Emo were only marginally influenced by the peptidic [D-Lys 6 ]GnRH carrier. ¶Posted on the website on

Mesoporous silica nanoparticles SBA-15 loaded with emodin upregulate the antioxidative defense of Euproctis chrysorrhoea (L.) larvae

“…Thus, when EO reaches the cell it can undergo oxidation or reduction reactions. As mentioned previously, the reduction of EO initially yields its semiquinone, which can generate the superoxide anion (O 2 .-) in the presence of oxygen due to electron transfer from the semiquinone to molecular oxygen (Rahimipour et al, 2001). Almost any oxidation of phenolics in the gut can generate O 2 .…”

“…By interacting with enzymes, transporters, channels, and receptors, EO has access to multiple cellular targets and can interfere with many pathways, which is a common feature of many plant phenolics (Mueller et al, 1998;Srinivas et al, 2007 and references therein;Teng et al, 2012;Dong et al, 2016). As a quinone, EO has a marked oxidative impact on the cellular redox status and on the generation of reactive oxygen species (ROS) (Rahimipour et al, 2001;Srinivas et al, 2007;Mecklenburg et al, 2009;Martín-Cordero et al, 2012;Qu et al, 2013;Liu et al, 2015;Lennicke et al, 2016). EO can be reduced to its semiquinone, which in the presence of molecular oxygen generates the superoxide anion (O 2 al., 2009;Lennicke et al, 2016).…”

Antitumor Activities of an Anthraquinone Fraction Isolated From In Vitro Cultures of Ophiorrhiza rugosa var decumbens

“…Previous workers have shown that electron paramagnetic resonance and electrochemical studies of AQ such as emodin could be easily reduced to semiquinone form and in the presence of oxygen and the semiquinones generate ROS, mainly superoxide. 30 Intracellular increase in ROS often leads to apoptosis, which is considered to be the mechanism of action of cytotoxicity in cancer cells mediated by AQs. 31 Anti-inflammatory activity was observed in AQf-treated groups.…”

Botanical Dietary Supplements Gone Bad

“…The mechanism of toxicity of 1,8-dihydroxyanthraquinones, such as emodin, likely involves redox cycling between the quinone and the semiquinone radical generating reactive oxygen species (ROS) resulting in lipid peroxidation, protein damage, and DNA oxidation ( Figure 2) (26,29,30). For example, treatment of Reuber hepatoma and fibroblast Balb/3T3 cells with various anthraquinones resulted in the formation of 8-oxo-dG (26).…”