BACKGROUND: One of the most promising strategies to overcome multidrug resistance (MDR) is to use compounds that can modulate P-glycoprotein and restore the cytotoxicity of anticancer drugs. Furthermore, the search for compounds that regulate and overcome apoptosis deficiency of cancer cells is also of great therapeutic importance. MATERIALS AND METHODS: Seven known pentacyclic triterpenes and one steroid were isolated from Euphorbia lagascae methanolic extracts and identified by physical and spectroscopic methods. These compounds, together with eleven terpenoids previously isolated from Euphorbia lagascae and E. tuckeyana were tested for their MDR-reversing and/or apoptosis induction activities by flow cytometry on L5178 human MDR1 gene-transfected mouse lymphoma cells. RESULTS: Four taraxastane-type triterpenes: 21alpha-hydroxytaraxasterol, 21alpha-hydroxytaraxasterol acetate, 3beta,30-dihydroxy-20(21)-taraxastene and 3beta-hydroxy-20-taraxasten-30-al, and two steroids: stigmastane-3,6-dione and ergosterol peroxide exhibited a significant MDR-Pgp modulation activity. Some aspects of structure-activity relationships are discussed. Regarding apoptosis induction, the most significant results were obtained for the polycyclic diterpenes ent-16alpha,17-dihydroxykauran-3-one and ent-16alpha,17-dihydroxyatisan-3-one.
BACKGROUND: One of the most promising strategies to overcome multidrug resistance (MDR) is to use compounds that can modulate P-glycoprotein and restore the cytotoxicity of anticancer drugs. Furthermore, the search for compounds that regulate and overcome apoptosis deficiency of cancer cells is also of great therapeutic importance. MATERIALS AND METHODS: Seven known pentacyclic triterpenes and one steroid were isolated from Euphorbia lagascae methanolic extracts and identified by physical and spectroscopic methods. These compounds, together with eleven terpenoids previously isolated from Euphorbia lagascae and E. tuckeyana were tested for their MDR-reversing and/or apoptosis induction activities by flow cytometry on L5178 humanMDR1 gene-transfected mouse lymphoma cells. RESULTS: Four taraxastane-type triterpenes: 21alpha-hydroxytaraxasterol, 21alpha-hydroxytaraxasterol acetate, 3beta,30-dihydroxy-20(21)-taraxastene and 3beta-hydroxy-20-taraxasten-30-al, and two steroids: stigmastane-3,6-dione and ergosterol peroxide exhibited a significant MDR-Pgp modulation activity. Some aspects of structure-activity relationships are discussed. Regarding apoptosis induction, the most significant results were obtained for the polycyclicditerpenes ent-16alpha,17-dihydroxykauran-3-one and ent-16alpha,17-dihydroxyatisan-3-one.
Authors: Alaa H Abuznait; Hisham Qosa; Nicholas D O'Connell; Jessica Akbarian-Tefaghi; Paul W Sylvester; Khalid A El Sayed; Amal Kaddoumi Journal: Food Chem Toxicol Date: 2011-08-10 Impact factor: 6.023
Authors: Essam H Ibrahim; Mona Kilany; Osama M S Mostafa; Kamel H Shaker; Mohammed Alshehri; Khalid M Alsyaad; Ali Alshehri; Khalid Ali Khan; Muhammad Qasim; Nahla Kotb; Abeer S Alahmari; Hamed A Ghramh; Saad M Dajem Journal: Saudi J Biol Sci Date: 2018-08-18 Impact factor: 4.219