Agustina D R Nurcahyanti1, Michael Wink2. 1. Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany. Electronic address: adr.nurcahyanti@gmail.com. 2. Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany. Electronic address: wink@uni-heidelberg.de.
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. PURPOSE: 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. MATERIAL AND 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. CONCLUSION: 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.
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. PURPOSE: 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. MATERIAL AND 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. CONCLUSION: 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: Zachary M Smith; Vincent Steinmetz; Jonathan Martens; Jos Oomens; John C Poutsma Journal: Int J Mass Spectrom Date: 2017-09-04 Impact factor: 1.986