Abstract
Phenanthriplatin is a new monofunctional platinum(II) complex that binds only one strand of DNA and acts by blocking gene transcription, but its effect on gene regulation has not been characterized relative to the traditional platinum-based complex, cisplatin. A549 non-small cell lung cancer and IMR90 lung fibroblast cells were treated with cisplatin, phenanthriplatin, or a control and then their RNA transcripts were subjected to next generation sequencing analysis. DESeq2 and CuffDiff2 were used to identify up- and downregulated genes and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were used to identify pathways and functions. We found that phenanthriplatin may regulate the genes GPRC5a, TFF1, and TNFRSF10D, which act through p53 to control apoptosis, differently or to a greater extent than cisplatin, and that it, unlike cisplatin, could upregulate ATP5MD, a gene which signals through the Wnt/β catenin pathway. Furthermore, phenanthriplatin caused unique or enhanced effects compared to cisplatin on genes regulating the cytoskeleton, cell migration, and proliferation, e.g., AGAP1, DIAPH2, GDF15, and THSD1 (p < 0.05; q < 0.05). Phenanthriplatin may modulate some oncogenes differently than cisplatin potentially leading to improved clinical outcome, but this monofunctional complex should be carefully matched with cancer gene data to be successfully applied in chemotherapy.
Highlights
The platinum(II) chemotherapy drug, cis-diamminedichloroplatinum(II) is a bifunctional complex with two chloride leaving ligands which typically forms intrastrand crosslinks with DNA resulting in altered gene transcription [1,2] (Figure 1)
Cells 2020, 9, 2637 can cause apoptosis in non-cancerous cells leading to severe side-effects by damaging renal, auditory and nervous system tissue and activate chemotherapy resistance mechanisms that cause apoptosis in non-cancerous cells leading to severe side-effects by damaging renal, auditory and prevent its anti-cancer activity [1,10,11]
DESeq2 and Cuffdiff2 analysis was performed on generation sequencing samples to obtain differentially expressed gene (DEG) profiles in phenanthriplatin, cisplatin, and control treated A549 and
Summary
The platinum(II) chemotherapy drug, cis-diamminedichloroplatinum(II) (cisplatin) is a bifunctional complex with two chloride leaving ligands which typically forms intrastrand crosslinks with DNA resulting in altered gene transcription [1,2] (Figure 1). Cells 2020, 9, 2637 can cause apoptosis in non-cancerous cells leading to severe side-effects by damaging renal, auditory and nervous system tissue and activate chemotherapy resistance mechanisms that cause apoptosis in non-cancerous cells leading to severe side-effects by damaging renal, auditory and prevent its anti-cancer activity [1,10,11]. Nervous system tissue and activate chemotherapy resistance mechanisms that prevent its anti-cancer activity [1,10,11]. Cisplatin is a DNA bifunctional complex whose anticancer activity isofprimarily related its ability to intercalate and distort leading platinum(II)
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