title: New anti-cancer characteristics of jatrophane diterpenes from Euphorbia dendroides.
abstract: Jatrophane diterpenes were shown to be inhibitors of P-glycoprotein (P-gp). There are also evidences on their microtubule-interacting activity in cancer cells. We evaluated new anti-cancer characteristics of two jatrophane type compounds from Euphorbia dendroides. For that purpose, the model system of sensitive non-small cell lung cancer cell line (NCI-H460) and its resistant counterpart (NCI-H460/R) was used. Although both jatrophanes showed inhibitory effect on cancer cell growth, they were non-toxic for peripheral blood mononuclear cells (PBMC). We examined their effects in combination with paclitaxel (PTX), a well-known mitotic spindle interacting chemotherapeutic. Jatrophanes overcome PTX resistance in concentration-dependent manner in MDR cancer cell line (NCI-H460/R). We observed that this synergistic effect is not caused merely by P-gp inhibition. In combination with PTX, jatrophanes induce cell killing and change cell cycle distribution leading to G2/M arrest. Furthermore, they exert an anti-angiogenic effect by decreasing the vascular endothelial growth factor (VEGF) secretion. The reduction of the level of mdr1 mRNA expression in sensitive cells, suggests that these compounds could not contribute to the development of resistance. In conclusion, present study provides a rational basis for the new cancer treatment approach with jatrophanes that are non-toxic to normal cells and have new favorable anti-cancer characteristics.
authors: Institute for Biological Research, Department of Neurobiology, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia. vtbvtm@sbb.rs
authors: Milica
authors: M
authors: Pešić
authors: Jasna
authors: J
authors: Banković
authors: Ivana S
authors: IS
authors: Aljančić
authors: Nina M
authors: NM
authors: Todorović
authors: Milka
authors: M
authors: Jadranin
authors: Vlatka E
authors: VE
authors: Vajs
authors: Vele V
authors: VV
authors: Tešević
authors: Ivan
authors: I
authors: Vučković
authors: Miljana
authors: M
authors: Momčilović
authors: Ivanka D
authors: ID
authors: Marković
authors: Nikola
authors: N
authors: Tanić
authors: Sabera
authors: S
authors: Ruždijić
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects; D004357:Drug Synergism; D028481:Euphorbia / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics; D017239:Paclitaxel / Q000627:therapeutic use; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D010936:Plant Extracts; D012333:RNA, Messenger; D042442:Vascular Endothelial Growth Factors; C530345:jatrophane; D017239:Paclitaxel