Publications by authors named "Laura Stultz"
Low solubility in aqueous solutions is a significant limitation of the otherwise promising anticancer ruthenium complex KP1019. In laboratory studies, this challenge is often overcome by using DMSO to help drive the drug into solution. Since DMSO was previously shown to alter the bioactivity of platinum-based chemotherapeutics, here we examine DMSO's effects on KP1019.
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- KP1019, a ruthenium-based anticancer complex, damages DNA and induces apoptosis like platinum-based chemotherapeutics but shows no dose-limiting toxicity in clinical trials.
- A proteomic study in yeast revealed that KP1019 likely causes oxidative stress by increasing antioxidant glutathione levels and altering protein expression involved in ribosome biogenesis and translation.
- Findings suggest that in addition to DNA damage, KP1019 also targets protein metabolism, indicating potential for combination therapies with other drugs like oxaliplatin.
Article Synopsis
- Careful regulation of the cell cycle is crucial for DNA replication, cell division, and repair, with DNA damage often causing delays that allow for repair processes.
- The anticancer drug KP1019 interacts with DNA and shows cytotoxic effects in cancer cells, and research in budding yeast indicates that it triggers a DNA damage response by inducing cell cycle arrest and mutations.
- Investigations reveal that KP1019 not only delays cell cycle progression but also causes abnormal nuclear positioning and spindle misalignment, linking the DNA damage response to both nuclear and motor protein activity changes in the cell.
The anticancer ruthenium complex trans-[tetrachlorobis(1H-indazole)ruthenate(III)], otherwise known as KP1019, has previously been shown to inhibit proliferation of ovarian tumor cells, induce DNA damage and apoptosis in colon carcinoma cells, and reduce tumor size in animal models. Notably, no dose-limiting toxicity was observed in a Phase I clinical trial. Despite these successes, KP1019's precise mechanism of action remains poorly understood.
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