gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

Antitumoral activity of the novel antitumoral compound CLU-502, isolated from Clusia rosea, in neuroblastoma and leukemia cell lines

Meeting Abstract

  • corresponding author presenting/speaker David Diaz-Carballo - Universitätsklinikum, Essen, Deutschland
  • Ralf A. Hilger - Universitätsklinikum, Essen
  • Sascha Malak - Universitätsklinikum, Essen
  • Dirk Strumberg - Universitätsklinikum, Essen
  • Siegfried Seeber - Universitätsklinikum, Essen

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO446

The electronic version of this article is the complete one and can be found online at:

Published: March 20, 2006

© 2006 Diaz-Carballo et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



We have characterized a polyisoprenylated benzophenone isolated from Clusia rosea, collected in Florida, USA. This novel substance, called CLU-502, was isolated from methanolic extracts of the plant using RP-HPLC coupled to a PDA-detector. In the SRB proliferation assay, CLU-502 demonstrated a potent cytotoxic activity in a panel of human tumor cell lines such as neuroblastoma and leukemia. Both, wild-type cell lines and sub-lines resistant to doxorubicin, cis-platin, etoposide or 5-fluorouracil were highly sensitive to CLU-502. Interestingly, normal fibroblasts were more resistant to this compound than cancer cells. CLU-502 inhibits the unwinding activity of topoisomerase I in a relaxation of pBR322l plasmid, as well as the decatenation of kinetoplasmids by human topoisomerase II. In addition, CLU-502 induce a dose-dependent inhibition of telomerase activity in vitro. A dose-dependent effect on the phosphorylation of ERK1/2, the cytosolic downstream enzymes of the MAP-kinase pathway, was also detected in Western blot analyses. The interaction of CLU-502 with PD98059, a specific inhibitor of ERK1/2 phosphorylation, resulted in a synergistic cytotoxic effect when both drugs were administered to tumor cells simultaneously. As the result of the exposure of cell cultures to CLU-502, a cell cycle arrest of the G1 phase was detected. Finally, an apoptosis/DNA-damage in tumor cells was observed in agarose gels after the exposure of CLU-502 at different concentrations. CLU-502 inhibits Akt/PKB in NB cells. Initial toxicological studies in a nude mouse model revealed that treatment with CLU-502 was well tolerated up to 100 mg/kg. The antitumoral effect are currently analyzed in vivo in a neuroblastoma nude mouse model.