Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells.
Leonardo Marques da FonsecaLucas Rodrigues Jacques da SilvaJhenifer Santos Dos ReisMarcos André Rodrigues da Costa SantosVictoria de Sousa ChavesKelli Monteiro da CostaJulliana de Nazareth Sa-DinizCelio Geraldo Freire de LimaAlexandre MorrotTatiany Nunes FranklimDouglas Chaves de Alcântara-PintoMarco Edilson Freire de LimaJose Osvaldo PreviatoLucia Mendonça PreviatoLeonardo Freire-de-LimaPublished in: Medicines (Basel, Switzerland) (2020)
Background: 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. Conclusions: These results suggest that piperine might be further used in therapeutic strategies for metastatic cancer and EMT-related disorders.
Keyphrases
- epithelial mesenchymal transition
- transforming growth factor
- signaling pathway
- gene expression
- induced apoptosis
- high throughput
- cell cycle arrest
- squamous cell carcinoma
- pi k akt
- single cell
- endothelial cells
- real time pcr
- dna methylation
- small cell lung cancer
- wound healing
- atomic force microscopy
- cell proliferation
- cell death
- pseudomonas aeruginosa
- induced pluripotent stem cells
- oxidative stress
- stem cells
- radiation therapy
- diabetic rats
- locally advanced
- protein kinase
- bone marrow
- cell migration
- anti inflammatory
- candida albicans
- combination therapy