Multidrug Resistance Modulation and Apoptosis Induction of Cancer Cells by Terpenic Compounds Isolated from Euphorbia Species

• Published in: Anticancer research Vol. 29; no. 11; pp. 4467 - 4472
• Main Authors: Duarte, Noélia, Ramalhete, Cátia, Varga, Andras, Molnár, Joseph, Ferreira, Maria-José U
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01-11-2009
• Subjects: Animals; Apoptosis - drug effects; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Euphorbia - chemistry; Humans; Leukemia L5178 - drug therapy; Leukemia L5178 - genetics; Leukemia L5178 - metabolism; Leukemia L5178 - pathology; Mice; Terpenes - isolation & purification; Terpenes - pharmacology
• ISSN: 0250-7005; 1791-7530

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: 21α-hydroxytaraxasterol, 21α-hydroxytaraxasterol acetate,
3β,30-dihydroxy-20(21)-taraxastene and 3β-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-16α,17-dihydroxykauran-3-one
and ent-16α,17-dihydroxyatisan-3-one.