Skip to main content

Cytotoxicity of aphidicolin and its derivatives against neuroblastoma cells in vitro: synergism with doxorubicin and vincristine.

Michaelis, Martin, Vogel, Jens-Uwe, Cinatl, Jindrich, Langer, Klaus, Kreuter, Jörg, Schwabe, Dirk, Driever, Pablo Hernáiz, Cinatl, Jaroslav (2000) Cytotoxicity of aphidicolin and its derivatives against neuroblastoma cells in vitro: synergism with doxorubicin and vincristine. Anti-cancer drugs, 11 (6). pp. 479-85. ISSN 0959-4973. (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)

Abstract

Disseminated neuroblastoma diseases are still indicated by a poor outcome despite treatment regimens including radiation therapy and high-dose chemotherapy with stem cell rescue. Therefore, new substances and treatment regimens are of interest. Aphidicolin (APH), a tetracyclic diterpene antibiotic produced by Cephalosporium aphidicola, has a specific toxicity for neuroblastoma cells. Furthermore, it was shown to enhance the effects of X-ray radiation and chemotherapy on malignant cells. To find new substances, 20 APH derivatives were tested for their anti-neuroblastoma efficacy in vitro in UKF-NB-2 cells. Five derivatives had antitumoral activity in neuroblastoma cells. A relationship between the structure and the antitumoral efficacy showed that the hydroxyl groups at C-3 and C-18 are essential for the antitumoral effects. Furthermore, antitumoral effects of APH in combination with doxorubicin and vincristine, both part of commonly used treatment regimens for disseminated neuroblastoma diseases, were tested in the neuroblastoma cell line UKF-NB-2. APH was found to act synergistically with vincristine and synergistically to additive with doxorubicin depending on the molecular ratio of the substances in combination. This may offer the chance to use APH and its derivatives as additional tools in the treatment of neuroblastomas.

Item Type: Article
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Martin Michaelis
Date Deposited: 05 Jun 2013 20:02 UTC
Last Modified: 29 May 2019 10:15 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/34129 (The current URI for this page, for reference purposes)
  • Depositors only (login required):