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. 2019 Dec;46(6):6071-6078.
doi: 10.1007/s11033-019-05042-9. Epub 2019 Aug 27.

Molecular pathways related to the control of proliferation and cell death in 786-O cells treated with plumbagin

Igor Alves Mancilla  1 , Giuliana Castello Coatti  2 , Bruna Isabela Biazi  1 , Thalita Alves Zanetti  1 , Adrivanio Baranoski  1 , Lilian Areal Marques  1 , Amanda Cristina Corveloni  1 , Sandra Regina Lepri  1 , Mario Sergio Mantovani  3
Affiliations

Molecular pathways related to the control of proliferation and cell death in 786-O cells treated with plumbagin

Igor Alves Mancilla et al. Mol Biol Rep. 2019 Dec.

Abstract

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.

Keywords: Antiproliferative; Apoptosis; Cell cycle; Cytotoxicity; DNA damage; Gene expression.

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