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New anti-cancer characteristics of jatrophane diterpenes from Euphorbia dendroides

Authorized Users Only
2011
Authors
Pešić, Milica
Bankovic, Jasna
Aljančić, Ivana
Todorović, Nina
Jadranin, Milka
Vajs, Vlatka
Tešević, Vele
Vučković, Ivan
Momcilovic, Miljana
Markovic, Ivanka D.
Tanic, Nikola
Ruzdijic, Sabera
Article (Published version)
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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, the...y 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.

Keywords:
Jatrophane / Spurge / Multi-drug resistance (MDR) / Paclitaxel / Apoptosis / Vascular endothelial growth factor (VEGF)
Source:
Food and Chemical Toxicology, 2011, 49, 12, 3165-3173
Publisher:
  • Pergamon-Elsevier Science Ltd, Oxford
Projects:
  • Identification of predictive molecular markers for cancer progression, response to therapy and disease outcome (RS-41031)
  • Natural products of wild, cultivated and edible plants: structure and bioactivity determination (RS-172053)

DOI: 10.1016/j.fct.2011.09.035

ISSN: 0278-6915

PubMed: 21996302

WoS: 000298202400023

Scopus: 2-s2.0-80054874373
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URI
http://cer.ihtm.bg.ac.rs/handle/123456789/830
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