Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells

• Published in: Medicines (Basel, Switzerland) Switzerland), 2020-04, Vol.7 (4), p.19
• Main Authors: Marques da Fonseca, Leonardo, Jacques da Silva, Lucas Rodrigues, Santos Dos Reis, Jhenifer, Rodrigues da Costa Santos, Marcos André, de Sousa Chaves, Victoria, Monteiro da Costa, Kelli, Sa-Diniz, Julliana de Nazareth, Freire de Lima, Celio Geraldo, Morrot, Alexandre, Nunes Franklim, Tatiany, de Alcântara-Pinto, Douglas Chaves, Freire de Lima, Marco Edilson, Previato, Jose Osvaldo, Mendonça-Previato, Lucia, Freire-de-Lima, Leonardo
• Format: Article
• Language: English
• Subjects: cancer; epithelial–mesenchymal transition; ERK1/2; piperidinyl amide; piperine; SMAD
• ISSN: 2305-6320; 2305-6320
• DOI: 10.3390/medicines7040019

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. 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. 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. These results suggest that piperine might be further used in therapeutic strategies for metastatic cancer and EMT-related disorders.