JJBS Volume 2, Number 1, March. 2009 ISSN 1995-6673 Pages 9 - 14 Jordan Journal of Biological Sciences Datura Aqueous Leaf Extract Enhances Cytotoxicity via Metabolic Oxidative Stress on Different Human Cancer Cells Iman M. Ahmad a,* , Maher Y. Abdalla b , Noor H. Mustafa b , Esam Y. Qnais b , Fuad A. Abdulla c a Dept. of Radiography, b Dept. of Biological Sciences and Biotechnology, The Hashemite University, Zarqa, Jordan; c Dept. of Physical Therapy, School of Health professions, Behavioral and Life Sciences, New York Institute of Technology, Amman, Jordan. Abstract اﻟﻤﻠﺨﺺ This study was designed to evaluate the cytotoxic effect ﻧﺒﺘﺔ ﻷوراق اﻟﻤﺎﺋﻲ اﻟﻤﺴﺘﺨﻠﺺ ﺳﻤﻴﺔ ﻣﺪى ﻟﺘﻘﻴﻢ اﻟﺪراﺳﺔ هﺬﻩ ﺻﻤﻤﺖ ﺧﻼﻳﺎ ﺮضMDA-MB231 وFaDu ﻟﻠﻤﺪة اﻟﺴﺮﻃﺎﻧﻴﺔ اﻟﺨﻼﻳﺎ ﺎﻟﺠﺔ ﻓﻲ ﺑﺎﺿﻄﺮاﺑﺎت اﻟﻤﺴﺘﺨﻠﺺ ﺑﻬﺬا ﻤﺴﺘﺨﻠ ﺺ اﻟﻤ ﻧﺒﺘﺔ ﻷوراق ﺎﺋﻲ © 2009 Jordan Journal of Biological Sciences. All rights reserved Keywords: Datura Stramonium; Glutathione; Mnsod; HO-1. of aqueous Datura stramonium leaf extract on different human cancer cell lines in vitro. Breast (MDA-MB231), head, neck (FaDu), and lung (A549) cancer cell lines were treated with 1 mg/ mL of Datura aqueous extract for 24 and 48 hours. Exposure of MDA-MB231 and FaDu cells to the extract for 24 hours resulted in a significant decrease in cell survival. Same effect was seen with all cell lines exposed to the Datura aqueous extract for 48 hours. Treatment with Datura aqueous extract also caused perturbations in parameters indicative of oxidative stress, including increased glutathione disulfide (GSSG) in FaDu cells treated for 48 hours. Additionally, an increase on the redox sensitive enzymes was seen in MnSOD and HO-1 on A549 cells, treated with Datura aqueous extract for 24 and 48 hours. The results may suggest therapeutic potential of Datura aqueous leaf extract for the treatment of different types of cancer. Further investigations are needed to verify whether this cytotoxic effect occurs in vivo. اﺳﺘﺮاﻣﻮﻧﻴﻮم اﻟﺪاﺗﻮرة) Datura stramonium ( ﺳﻼﻻت ﻣﻦ اﻟﻌﺪﻳﺪ ﻋﻠﻰ اﻟﺴﺮﻃﺎﻧﻴﺔ اﻹﻧﺴﺎن ﺧﻼﻳﺎ, ﺧﻼﻳﺎ ﺑﺘﻌﺮﻳﺾ ﻗﻤﻨﺎ اﻟﻬﺪف هﺬا ﻟﺘﺤﻘﻴﻖ اﻟﺜﺪي ﺳﺮﻃﺎن) ,(MDA-MB231 واﻟﺮﻗﺒﺔ اﻟﺮأس) FaDu ( وﺳﺮﻃﺎن اﻟﺮﺋﺔ) A549 ( اﻟﻤ ﻓﻲ ﻟﺘﺮآﻴﺰ ﺨﺘﺒﺮ) 1 ﻣﻐﻢ\ ﻣﻞ( هﺬﻩ ﻣﺴﺘﺨﻠﺺ ﻣﻦ اﻟﻨﺒﺘ ﺔ ﻟﻤﺪة24 و48 ﺳﺎﻋﺔ. ﺗﻌ ﺑﻌﺪ اﻧﻪ اﻟﻨﺘﺎﺋﺞ ﻣﻦ اﺗﻀﺢ 24 اﻟﺤﻴﺔ اﻟﺨﻼﻳﺎ ﻋﺪد ﻓﻲ ﻣﻠﺤﻮظ اﻧﺨﻔﺎض ﺳﺎﻋﺔ, ﻧﻔﺲ ﻣﻼﺣﻈﺔ ﺗﻢ وﻗﺪ ﻟﻤﺪة ﻟﻠﻤﺴﺘﺨﻠﺺ ﺗﻌﺮﺿﻬﺎ ﺑﻌﺪ اﻟﺨﻼﻳﺎ أﻧﻮاع ﺟﻤﻴﻊ ﻋﻠﻰ اﻟﺘﺄﺛﻴﺮ48 ﺳﺎﻋﺔ. ﻣﻌ وأﺳﻔﺮ ﻣﻌﺎ اﻟﻤﺆآﺴﺪ اﻟﺠﻠﻮﺗﺎﺛﻴﻮن ﻧﺴﺒﺔ زﻳﺎدة ذﻟﻚ ﻓﻲ ﺑﻤﺎ اﻷآﺴﺪة ﺟﻬﺪ ﻳﻴﺮ )) glutathione disulfide (GSSG ( , إﻧﺰﻳﻤﺎت زﻳﺎدة إﻟﻰ ﺑﺎﻹﺿﺎﻓﺔ ﻣﺜﻞ اﻷآﺴﺪة ﺟﻬﺪMnSOD , HO-1 . اﻟ إﺳﺘﺨﺪام ﻳﻤﻜﻦ أﻧﻪ إﻟﻰ اﻟﻨﺘﺎﺋﺞ هﺬﻩ ﺗﺸﻴﺮ اﺳﺘﺮاﻣﻮﻧﻴﻮم اﻟﺪاﺗﻮرة) Datura stramonium ( ﻣﻦ ﻣﺨﺘﻠﻔﺔ أﻧﻮاع ﻟﻌﻼج ﺣﻴﺜﻴﺔ ﻟﻤﻌﺮﻓﺔ اﻟﺘﺠﺎرب ﻣﻦ اﻟﻤﺰﻳﺪ إﺟﺮاء ﺑﻌﺪ اﻹﻧﺴﺎن ﻓﻲ اﻟﺴﺮﻃﺎن اﻹﻧﺴﺎن ﻓﻲ اﻟﻤﺮآﺐ هﺬا ﻋﻤﻞ. 1. Introduction * 1.1. Plant stramonium, more commonly known as jimson we Datura ed or thorn apple, is a wild-growing flowering plant belonging to the family Solanaceae and is a medicinal plant with antinociceptive (Abdollahi et al., 2003) antioxidant (Couladis et al., 2003), hypolipidemic (Rasekh et al., 2001), anti-inflammatory, anti-rheumatoid (Tariq et al., 1989), and hypoglycemic (Gharaibeh et al., 1988) properties. Therefore, this study was carried out to evaluate the therapeutic potential of the aqueous Datura stramonium leaf extract in the treatment of different types of cancer. 1.2. Oxidative Stress continuously produce reactive ox * Corresponding author. iman_maher@yahoo.com. Mammalian cells ygen species (ROS) through various metabolic pathways. Reactive oxygen species are molecules that contain oxygen and have higher reactivity than ground- state molecular oxygen. These species include not only the oxygen radicals (like O 2 •- , • OH, and peroxyl radicals), but also non-radical molecules such as H 2 O 2 and 1 O 2 . Superoxide is formed during the reduction of O 2 by the mitochondrial electron transport system (Boveris and Cadenas, 1982). Eukaryotic cells are equipped with an antioxidant system capable of converting ROS to H 2 O via different cytosolic enzymes. Oxidative stress results when the balance between the production of ROS exceeds the antioxidant capability of the target cell. It is generally thought that low levels of ROS are not harmful to cells, and indeed even perform useful signaling functions, whereas high levels of ROS are detrimental through covalent reactions with cellular proteins, lipids, and DNA that results in altered target molecule function. The accumulation of oxidative damage has been implicated in