Comparative analyses of cytotoxicity and molecular mechanisms between platinum metallointercalators and cisplatin.

Shaoyu Wang, Ming Wu, Vincent Higgins, J R Aldrich-Wright

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Platinum(ii) metallointercalators of the type [Pt(IL)(AL)]2+, such as [(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(ii)]2+ (56MESS), are structurally different from cisplatin. This study, using a comparative transcriptomics approach, uncovered genomic expression patterns and molecular pathways that distinctively differentiated 56MESS and cisplatin in the eukaryote model organism Saccharomyces cerevisiae (yeast). Down-regulation of sulfur assimilation, cellular respiration, and energy metabolism were characteristics of 56MESS while up-regulation of these pathways and genes in cell cycle was the action of cisplatin. Furthermore, de novo purine biosynthesis and glycine metabolism were induced by 56MESS but suppressed by cisplatin. Different effects on intracellular concentrations of iron and copper were evident, with 56MESS more profoundly inducing genes controlling uptake of these ions than cisplatin. Finally, apart from 56MESS, additional metallointercalators including 56MEEN, 5MERR and 5MESS were subsequently identified to be more active in a cisplatin-resistant mouse leukaemia L1210cisR cell line than cisplatin, which provides multiple lead compounds for future drug development.
Original languageEnglish
Pages (from-to)950-959
Number of pages10
JournalMetallomics
Volume4
Issue number9
DOIs
Publication statusPublished - 2012

Fingerprint

Dive into the research topics of 'Comparative analyses of cytotoxicity and molecular mechanisms between platinum metallointercalators and cisplatin.'. Together they form a unique fingerprint.

Cite this