Differences in cisplatin distribution in sensitive and resistant ovarian cancer cells: a TEM/NanoSIMS study

Abstract

Cisplatin is a widely used anti-cancer drug, but its effect is often limited by acquired resistance to the compound during treatment. Here, we use a combination of transmission electron microscopy (TEM) and nanoscale-secondary ion mass spectrometry (NanoSIMS) to reveal differences between cisplatin uptake in human ovarian cancers cells, which are known to be susceptible to acquired resistance to cisplatin. Both cisplatin sensitive and resistant cell lines were studied, revealing markedly less cisplatin in the resistant cell line. In cisplatin sensitive cells, Pt was seen to distribute diffusely in the cells with hotspots in the nucleolus, mitochondria, and autophagosomes. Inductively coupled plasma mass spectrometry (ICP-MS) was used to validate the NanoSIMS results.

Infrared nanospectroscopic mapping of a single metaphase chromosome

“…Transmission Electron Microscopy/nano Secondary Ions Mass Spectrometry (TEM/NanoSIMS) studies have confirmed an accumulation of concentrated Pt hotspots in nuclei of A2780 cells treated with cisplatin (88). Discrete foci in cellular nuclei have also been observed in other studies of cisplatin distribution in cancer cells (88–90).…”

Tracking the cargo of extracellular symbionts into host tissues with correlated electron microscopy and nanoscale secondary ion mass spectrometry imaging

“…Recent studies have indicated that the nucleolus is multifunctional, with roles in gene stability and silencing, cell‐cycle regulation, stress, and immune response (Boisvert, van Koningsbruggen, Navascues, & Lamond, ; Grummt, ). For example, recent NanoSIMS analyses have shown that cancer drugs, which influence these sorts of activities in the cell, showed strong stable‐isotope labelling in the nucleolus (Lee et al, ; Lee et al, ). Further, all processes of the above‐mentioned functions of the nucleolus are ones that are influenced by interactions with microbes.…”

Recent Considerations in the Application of RAPTA‐C for Cancer Treatment and Perspectives for Its Combination with Immunotherapies

“…[61,63] In this context, RAPTA-C was shown to upregulate reactive oxygen species in cancer cells induced by blockade of the mitochondrial and p53-Janus kinase (JNK) pathways. [27] However, metal-based compounds tend to bind to many different biomolecular targets, and while RAPTA compounds are more discriminating than, for example, platinum-based drugs due to their more complex 3D structure, certain targets appear to dominate, which has been reviewed by Murray et al [75,76] The related compound RAPTA-T containing a toluene ring harbors anti-metastatic activity inhibiting the invasive phenotype of cancerous cells by modulating the adhesive properties. [77] Further, RAPTA-T has been shown to induce allosteric binding of other drugs in the nucleosome core particle thereby mediating drug-drug synergies.…”

“…In this context, RAPTA‐C was shown to upregulate reactive oxygen species in cancer cells induced by blockade of the mitochondrial and p53‐Janus kinase (JNK) pathways . However, metal‐based compounds tend to bind to many different biomolecular targets, and while RAPTA compounds are more discriminating than, for example, platinum‐based drugs due to their more complex 3D structure, certain targets appear to dominate, which has been reviewed by Murray et al…”