Cellular pharmacology of mu-[1,2-bis(diphenylphosphino)ethane]bis[(1-thio-beta-D-gluco pyranosato-S)gold(I)]: a novel antitumor agent.

Abstract

SK&F 102912 (mu-[1,2-bis(diphenylphosphino)ethane]bis[(1-thio-beta-D- glucopyranosato-S)gold(I)], [(Autg)2(dppe)]) has shown reproducible and significant activity in transplantable murine tumor models and represents a structurally unique class of antineoplastic agents. A number of in vitro studies were performed to elucidate the cellular pharmacology of this gold-containing complex. [(Autg)2(dppe)] is a potent cytotoxic agent in vitro as demonstrated by its ability to inhibit the clonogenic capacity of a variety of tumor cell lines following a brief exposure to the drug. Cell-cycle analysis using HL-60 cells showed that low concentrations (2 microM) of [(Autg)2(dppe)] induced an S-phase block and higher concentrations induced a secondary block at the G1/S boundary. [(Autg)2(dppe)] had several effects on DNA metabolism and structure including preferential inhibition in cells of DNA synthesis (relative to RNA and protein synthesis) and the production of DNA single- and double-strand breaks as measured by alkaline elution. The cytoxic mechanism of this gold complex appears to be distinct from that of the monophosphine-gold complex auranofin.

• Authors: C K Mirabelli, B D Jensen, M R Mattern, C M Sung, S M Mong, D T Hill, S W Dean, P S Schein, R K Johnson, S T Crooke
• Journal: Anti-cancer drug design (Anticancer Drug Des) Vol. 1 Issue 3 Pg. 223-34 (Nov 1986) ISSN: 0266-9536 [Print] United States
• PMID: 3450295 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Chromatin
• Organometallic Compounds
• SK&F 102912
• Auranofin
• DNA

Topics

• Antineoplastic Agents (pharmacology)
• Auranofin (pharmacology)
• Cell Cycle (drug effects)
• Cell Survival (drug effects)
• Chromatin (drug effects)
• DNA (biosynthesis)
• DNA Damage
• Organometallic Compounds (pharmacology)
• Tumor Cells, Cultured (drug effects)