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: Milica Pešić, Jasna Banković, Ivana S Aljančić, Nina M Todorović, Milka Jadranin, Vlatka E Vajs, Vele V Tešević, Ivan Vučković, Miljana Momčilović, Ivanka D Marković, Nikola Tanić, Sabera Ruždijić
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 49 Issue 12 Pg. 3165-73 (Dec 2011) ISSN: 1873-6351 [Electronic] England
• PMID: 21996302 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• ABCB1 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antineoplastic Agents, Phytogenic
• Diterpenes
• Plant Extracts
• RNA, Messenger
• Vascular Endothelial Growth Factors
• jatrophane
• Paclitaxel

Topics

• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1 (antagonists & inhibitors, genetics, metabolism)
• Antineoplastic Agents, Phytogenic (pharmacology)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Diterpenes (pharmacology)
• Drug Resistance, Multiple (drug effects)
• Drug Synergism
• Euphorbia (chemistry)
• Gene Expression Regulation, Neoplastic
• Humans
• Leukocytes, Mononuclear (drug effects)
• Neoplasms (drug therapy, genetics)
• Paclitaxel (therapeutic use)
• Plant Extracts (pharmacology)
• RNA, Messenger (genetics, metabolism)
• Vascular Endothelial Growth Factors (metabolism)