Molecular pathways related to the control of proliferation and cell death in 786-O cells treated with plumbagin.
Igor Alves MancillaGiuliana Castello CoattiBruna Isabela BiaziThalita Alves ZanettiAdrivanio BaranoskiLilian Areal MarquesAmanda Cristina CorveloniSandra Regina LepriMario Sergio MantovaniPublished in: Molecular biology reports (2019)
Plumbagin (PLB) is a phytochemical being used for centuries in traditional medicines. Recently, its capacity to inhibit the development of human tumors has been observed, through the induction of apoptosis, cell cycle arrest, and inhibition of angiogenesis and metastasis. Here we evaluated the mechanism of action of PLB in the kidney adenocarcinoma 786-O cell line, which are metabolizing cells important for toxicology studies. After the treatment with PLB, we observed increased apoptosis and cell cycle arrest in S and G2/M phases, starting at 5 µM. In addition, PLB was cytotoxic, genotoxic and induced loss of cell membrane integrity. Regarding gene expression, treatment with 7.5 µM PLB reduced the amount of MTOR, BCL2 and ATM transcripts, and increased CDKN1A (p21) transcripts. Phosphorylation levels of yH2AX was increased and MDM2 protein level was reduced following the treatment with PLB, demonstrating its genotoxic effect. Our results suggest that PLB acts in molecular pathways related to the control of proliferation and cell death in 786-O cells.
Keyphrases
- cell cycle arrest
- cell death
- pi k akt
- gene expression
- signaling pathway
- endothelial cells
- cell proliferation
- dna damage
- combination therapy
- dna methylation
- replacement therapy
- induced apoptosis
- high glucose
- small molecule
- endoplasmic reticulum stress
- dna damage response
- binding protein
- single molecule
- rectal cancer
- case control
- protein protein
- anti inflammatory