BIAN N-Heterocyclic Gold Carbene Complexes induced cytotoxicity in human cancer cells via upregulating oxidative stress.

Muhammad Farooq,Daniel A Evans,Alan H Cowley,Rachel R Butorac,Nael Abu Taha,Mohammad Am Wadaan,Ahmed A Elzatahry

doi:10.7314/apjcp.2015.16.16.7003

Muhammad Farooq, Daniel A Evans + Show 5 more

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https://doi.org/10.7314/apjcp.2015.16.16.7003

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Abstract

Nanoparticles of gold and silver are offering revolutionary changes in the field of cancer therapy. N-heterocyclic carbene (NHC) metal complexes possess diverse biological activities and are being investigated as potential chemotherapeutic agents. The purpose of this study was to examine the cytotoxicity and possible mechanisms of action of two types of newly synthesized nanofiber composites containing BIAN N-heterocyclic gold carbene complexes in two types of human cancer cells, namely breast cancer (MCF7) and liver cancer (HepG2) cells and also in normal human embryonic kidney cells (HEK 293). Cytotoxicity was assessed by MTT cell viability assay and oxidative stress by checking the total glutathione level. Both compounds affected the cell survival of the tested cell lines at very low concentrations (IC50 values in the micro molar range) as compared to a well-known anti-cancer drug, 5 fluorouracil. A 60-80% depletion in total glutathione level was detected in treated cells. Reduction in total glutathione level is one of the biochemical pathways for the induction of oxidative stress which in turn could be a possible mechanism of action by which these compounds induce cytotoxicity in cancer cell lines. The in vitro toxicity towards cancer cells found here means that these molecules could be potential anticancer candidates.

Highlights

A carbene is a divalent carbon atom linked to two other groups by covalent bonds, and possesses two unshared valence electrons
We have previously reported the synthesis of nanofiber composite bis(imino)acenaphthene (BIAN) N-heterocyclic carbene (NHC) gold carbene complexes and their antimicrobial and antifungal activities (Butorac et al, 2011; Elzatahry et al, 2012)
~5 x103 cells were seeded in each well of a 12-well cell culture plate in high glucose Dulbecco’s Modified Eagle Medium (DMEM: Life technologies cat # 11995073) supplemented with 10% Fetal bovine serum (FBS: Life technologies cat # 16000044) in a humidified incubator with 5% CO2 at 37°C for 24 hours The various indicated concentrations of the compounds were added to wells in triplicate and the cells were cultured with these compounds for further 24 hours

Summary

Introduction

A carbene is a divalent carbon atom linked to two other groups by covalent bonds, and possesses two unshared valence electrons. These electrons can be paired in the same orbital as anti-parallel spins (singlet) represented as σ2 or pπ in different orbitals, or as parallel spins (triplet) represented as σ1 pπ. Conclusions: Reduction in total glutathione level is one of the biochemical pathways for the induction of oxidative stress which in turn could be a possible mechanism of action by which these compounds induce cytotoxicity in cancer cell lines. The in vitro toxicity towards cancer cells found here means that these molecules could be potential anticancer candidates

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