title: Cytotoxic potentiation of vinblastine and paclitaxel by L-canavanine in human cervical cancer and hepatocellular carcinoma cells.
abstract: BACKGROUND
  The non-protein amino acid L-canavanine (L-CAV), found in several plants of the family Fabaceae is an antimetabolite which shows anticancer activity due to its ability to be incorporated into protein in the place of its analogue, L-arginine (L-ARG), leading to the alteration of the 3D conformation of newly synthesised proteins and usually a loss of their function.
  
  
  OBJECTIVE
  In this study, the ability of L-CAV to potentiate the cytotoxicity of microtubule- targeting drugs used in the chemotherapy of cancer, vinblastine (VIN) and paclitaxel (PTX) was evaluated.
  
  
  METHODS
  The following cancer cells grown in arginine-rich and arginine-free media were employed: HeLa, Hep G2 and SK-HEP-1. Drug combination experiment used a method based on the median-effect principle and mass-action law.
  
  
  RESULTS
  We observed that L-CAV, which is hardly toxic alone, potentiated the cytotoxicity of VIN and PTX in HeLa and hepatocellular carcinoma cells.
  
  
  CONCLUSIONS
  This is the first study showing the cytotoxic potentiation of microtubule-targeting drugs by L-CAV. The mechanism of synergy and animal studies need to be investigated further to see whether L-CAV might become an adjuvant in cancer treatment.
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany. Electronic address: adr.nurcahyanti@gmail.com.
authors.forename: Agustina D R
authors.initials: AD
authors.lastname: Nurcahyanti
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany. Electronic address: wink@uni-heidelberg.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Wink
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001120:Arginine / Q000737:chemistry; D002172:Canavanine / Q000494:pharmacology*; D004357:Drug Synergism; D006367:HeLa Cells / Q000187:drug effects; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D014747:Vinblastine / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002172:Canavanine; D014747:Vinblastine; D001120:Arginine; D017239:Paclitaxel
keywords: Argininosuccinate synthase; L-canavanine; Microtubule; Paclitaxel; Synergy; Vinblastine