Multidrug resistance modulation and apoptosis induction of cancer cells by terpenic compounds isolated from Euphorbia species.
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.


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.
Duarte
Noélia
N
Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
Ramalhete
Cátia
C
Varga
Andras
A
Molnár
Joseph
J
Ferreira
Maria-José U
MJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D028481:Euphorbia / Q000737:chemistry*; D006801:Humans; D007940:Leukemia L5178 / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D013729:Terpenes / Q000302:isolation & purification / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D013729:Terpenes