Inhibitory effects of a new oral gold compound on hela cells

Abstract

Auranofin (AF), a recently introduced oral antirheumatic coordinated gold compound, was investigated for its antitumor potential. Due to certain similarities with the antitumor-coordinated compound, cis-Diamminedichloroplatinum II, we studied the effects of AF on cell proliferation. These studies included assessing DNA, RNA, and protein synthesis as measured by incorporation of 3H-thymidine, 3H-uridine, and 3H-leucine, respectively, into HeLa cells. AF was shown to exert a dose-dependent inhibition on DNA synthesis and to inhibit 3H-thymidine uptake more rapidly and persistently than 3H-uridine or 3H-leucine uptake at a gold concentration of 75--100 micrograms/dl. These three parameters were inhibited with a 24-hour exposure to 100 micrograms/dl. The inhibition of 3H-thymidine uptake in HeLa pretreated for 6 hours with 50 or 100 micrograms/dl of gold was found to be irreversible. No change in tracer uptake was observed in the acid-soluble pool or in the uptake of 3H-2-deoxy-D-glucose in these cells. Furthermore, HeLa cells demonstrated marked reductions in viability and oxygen uptake after exposure to AF. Dose-dependent surface morphological changes, e.g., blebbing, pitting, were noted in these cells after a brief treatment period. These results suggest this coordinated gold compount exerts a significant inhibitory effect on essential biological processes and functions.

An investigation into the interactions of gold nanoparticles and anti-arthritic drugs with macrophages, and their reactivity towards thioredoxin reductase

“…In addition, it has been speculated that the anti-cancer activity of auranofin may be linked to its ability to interact with TrxR [45,57]. Further interest in examining the binding of the various gold agents to this protein stems from the reported use of MALDI-MS to examine the binding interactions between TrxR and several different Au(I) complexes, including auranofin, aurothiomalate and AuPEt 3 Cl [27].…”

The reaction of chloro(triphenylphosphine)gold(I) with 1-methylthymine

“…4 The positions of peaks caused by the C(5'), C(1), and C(5) atoms change very little in the three compounds. The C(6) signal shows a significant upfield shift in the gold complex compared to the neutral and anionic species which is further evidence of the shielding power of electron density from the gold atom at the para position.…”

“…Unlike the other anti-arthritis gold drugs, auranofin has also shown evidence for anti-cancer activity in in vivo studies of P388 lymphocytic leukemia and sarcoma 180 tumors in mice (2)(3)(4). These results have prompted further investigation of the interaction of auranofin and analogous gold compounds with DNA both in vivo and irz vitro (5-7).…”

Applications and implications of gold therapy

“…Hence, the serious adverse reactions which have been encountered in the use of gold-sulphur complexes available so far may be avoided. In studies performed with proliferating lymphocyte and human cancer cells (African Burkitt's lymphoma and carcinoma of the cervix grown in the laboratory) the authors have also observed dramatic antiproliferative action by AF as reflected by the suppression of DNA, RNA and protein...synthesis (21,22) (Figures 8 and 9). We have observèd a gold dosedependent surface morphological change illustrated by blebbing and pitting not only in cancer cells, but also in lymphocytes obtained from patients receiving AF therapy (Figures 10 and 11).…”