RNA-Seq Analysis of Cisplatin and the Monofunctional Platinum(II) Complex, Phenanthriplatin, in A549 Non-Small Cell Lung Cancer and IMR90 Lung Fibroblast Cell Lines.

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.

• Authors: Jerry D Monroe, Satya A Moolani, Elvin N Irihamye, Joshua S Speed, Yann Gibert, Michael E Smith
• Journal: Cells (Cells) Vol. 9 Issue 12 (12 08 2020) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 33302475 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• ATF3 protein, human
• Activating Transcription Factor 3
• Coordination Complexes
• Organoplatinum Compounds
• Phenanthridines
• phenanthriplatin
• Platinum
• PFKFB3 protein, human
• Phosphofructokinase-2
• Cisplatin

Topics

• Activating Transcription Factor 3 (genetics, metabolism)
• Carcinoma, Non-Small-Cell Lung (metabolism, pathology)
• Cell Line
• Cisplatin (pharmacology)
• Coordination Complexes (chemistry, pharmacology)
• Down-Regulation (drug effects)
• Fibroblasts (cytology, drug effects, metabolism)
• Humans
• Lung (cytology, drug effects, metabolism)
• Lung Neoplasms (metabolism, pathology)
• Organoplatinum Compounds (pharmacology)
• Phenanthridines (pharmacology)
• Phosphofructokinase-2 (genetics, metabolism)
• Platinum (chemistry)
• Sequence Analysis, RNA
• Up-Regulation (drug effects)