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Scientific article
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Synergetic bitherapy in mice with xenografts of human prostate cancer using a methional mimic (METLICO) and an aldehyde dehydrogenase 3 inhibitor (MATE): systemic intraperitoneal (IP) and targeted intra-tumoral (IT) administration

Published inCurrent medicinal chemistry, vol. 16, no. 10, p. 1184-1191
Publication date2009
Abstract

An intraperitoneal (IP) monotherapy in nu/nu mice with subcutaneous xenografts of a human prostate epithelial cancer cell line:DU145 was undertaken with an aldehyde dehydrogenase 3 inhibitor MATE, that is a potent apoptogen on (DU145) in culture but not on their human prostate epithelial normal counterparts [13] . Tumour growth was slowed down but treatment had to be done 5days/week. To try to potentiate the action of MATE in vivo, a bitherapy was undertaken based on the synergetic apoptotic effect that had been observed previously in culture on DU145 treated with a methional mimic METLICO and DIMATE, an inhibitor of ALDH1 and ALDH3 [19]. The bitherapy with METLICO/MATE administered IP was as effective as the monotherapy with MATE alone by IP, but at a 2-fold lower dose of MATE and at a dose of METLICO that had no growth-inhibitory effect as a monotherapy . Hence there was definite synergism with bitherapy. To try to increase the efficacy of bitherapy, it was administered by the intra-tumoral (IT) route using the recently developed 20-bars-pressurized microinjection system from CERMA [16, 17]. IT administration of the bitherapy was indeed more effective than that by IP as regards tumour volumes are concerned. Histopathological analysis of IT-treated tumours confirmed that there were many necrotized zones but intact cells were still present. Approaches for treating a wider zone of tumour tissue by IT-bitherapy are discussed.

Keywords
  • Aldehyde Dehydrogenase/*antagonists & inhibitors
  • Aldehydes/administration & dosage/*chemistry/therapeutic use
  • Animals
  • *Biomimetics
  • Combined Modality Therapy
  • Drug Delivery Systems
  • Enzyme Inhibitors/administration & dosage/chemistry/*therapeutic use
  • Female
  • Humans
  • Injections, Intralesional
  • Injections, Intraperitoneal
  • Male
  • Mice
  • Mice, Nude
  • Molecular Structure
  • Morpholines/chemistry/*therapeutic use
  • Prostatic Neoplasms/*drug therapy/pathology
  • Quinazolines/chemistry/*therapeutic use
  • Tumor Burden
Citation (ISO format)
HILTBRAND, E. et al. Synergetic bitherapy in mice with xenografts of human prostate cancer using a methional mimic (METLICO) and an aldehyde dehydrogenase 3 inhibitor (MATE): systemic intraperitoneal (IP) and targeted intra-tumoral (IT) administration. In: Current medicinal chemistry, 2009, vol. 16, n° 10, p. 1184–1191. doi: 10.2174/092986709787846596
Identifiers
ISSN of the journal0929-8673
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