Distinct cellular fates for KP1019 and NAMI-A determined by X-ray fluorescence imaging of single cells

Abstract

Small molecule ruthenium complexes show great promise as anticancer pharmaceuticals, but further rational development of these as drugs is stymied by an incomplete understanding of the mechanisms that give rise to markedly different biological behaviour for structurally similar species. X-ray fluorescence imaging at two incident energies was used to reveal the intracellular distribution of Ru in single human cells treated with KP1019, showing Ru localised in both cytosol and in the nuclear region. In addition the imaging showed that treatment with KP1019 modulated Fe distribution to resemble the Ru distribution, without affecting cellular Fe content. In stark contrast, Ru could not be visualised in cells treated with NAMI-A, indicating that it was not internalised and supporting the proposition that its activity is exerted through a membrane-binding mechanism.

Anti‐cancer drug KP1019 modulates epigenetics and induces DNA damage response in Saccharomyces cerevisiae

“…S1a and S1b). The spectra obtained after mass spectrometric analysis of KP1019 were same as observed earlier [17].…”

“…Therefore, we employed various yeast histone tail mutants to investigate the effect of KP1019. Removal of N-terminal tail of H2A (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) or H3(1-30) leads to hypersensitivity to KP1019 (Fig. 3A) suggesting that these regions of histone tails are crucial for providing resistance to this drug.…”

Cytotoxic hydrogen bridged ruthenium quinaldamide complexes showing induced cancer cell death by apoptosis

“…[6][7][8][9][10][11][12][13][14][15][16] Ruthenium-based complexes are some of the most promising, with reported selective potency in vitro and in vivo. [17][18][19][20][21][22] McGowan et al have synthesised a range of ruthenium metal complexes for their uses as anticancer agents. [23][24][25][26] The work published on ruthenium quinaldamides showed that under inert atmosphere conditions, the filtering over NH4PF6 yielded the ruthenium quinaldamide monomers.…”

In Vivo Enzymes Activities of Some Ru(II) Compounds with N-Alkylphenothiazines

“…Many biological properties have been attributed to ruthenium complexes including antioxidant activity [12,13] and cytotoxicity [3,9,10]. Anticancer activities of Ru(II)-DMSO complexes are known for many years and some of them are in intensively clinical trials [14,15], while Ru(II)-arene complexes have been also widely studied as anticancerogenic compounds [3,16]. Previous investigations of enzyme activities of ruthenium complexes demonstrated a slight induction of superoxide dismutase (SOD) and catalase (CAT) in the rat liver tissue [17], but also an inhibition of succinate dehydrogenase (SDH) and cytochrome oxidase (COX) activities in the brain, heart, skeletal muscle, liver and kidney of rats [18].…”