Marques da Fonseca L, Jacques da Silva LR, Santos Dos Reis J, Rodrigues da Costa Santos MA, de Sousa Chaves V, Monteiro da Costa K, Sa-Diniz JN, Freire de Lima CG, Morrot A, Nunes Franklim T, de Alcântara-Pinto DC, Freire de Lima ME, Previato JO, Mendonça-Previato L, Freire-de-Lima L. Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells. Medicines (Basel). 2020 Apr 8;7(4):19.

DOI: https://doi.org/10.3390/medicines7040019

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Piperine, an amide extracted from the Piper spices, exhibits strong anti-tumor properties. However, its effect on the epithelial–mesenchymal transition (EMT) process has never been investigated. Herein, we evaluate the toxic effect of piperine on lung adenocarcinoma (A549), breast adenocarcinoma (MDA-MB-231) and hepatocellular carcinoma (HepG2) cell lines, as well as its ability to inhibit EMT-related events induced by TGF-β1 treatment. Methods: The cell viability was investigated by MTT assay. Protein expression was evaluated by Western blot. Gene expression was monitored by real-time PCR. Zymography assay was employed to detect metalloproteinase (MMP) activity in conditioned media. Cell motility was assessed by the wound-healing and phagokinetic gold sol assays. Results: The results revealed that piperine was cytotoxic in concentrations over 100 µM, showing IC50 values for HepG2, MDA-MB-231 and A549 cell lines of 214, 238 and 198 µM, respectively. In order to investigate whether piperine would reverse the TGF-β1 induced-EMT, the A549 cell line was pretreated with sublethal concentrations of the natural amide followed by the addition of TGF-β1. Besides disrupting EMT-related events, piperine also inhibited both ERK 1/2 and SMAD 2 phosphorylation.