Uncovering the Inhibitory Molecular Mechanism of Pomegranate Peel to Urinary Bladder Urothelial Carcinoma Using Proteomics Techniques.
Kuan-Hua HuangChing-Ping ChangLan-Hsiang ChienChien-Feng LiLing-Yu TangYu-Yi ChanTing-Feng WuPublished in: Life (Basel, Switzerland) (2022)
Pomegranate ( Punica granatum L.) fruit demonstrates the repressive effectiveness of many tumors. Our previous studies showed that the PEP (pomegranate peel extract) E2 fraction obtained from the ethyl acetate layer of the pomegranate peel's ethanol extract exhibited the highest inhibitory activities to induce Urinary bladder urothelial carcinoma (UBUC) cell apoptosis. The ethyl acetate layer could lower the volume and weight of T24 tumors and initiate apoptosis in nude mice xenografted bladder tumors. In this study, we intended to clarify the inhibitory molecular process of Taiwanese local pomegranate peel to urinary bladder urothelial carcinoma using a proteomics strategy. Gel-based proteomics (two-dimensional gel electrophoresis coupled with tandem mass spectrometry) was used to get an insight into the molecular mechanisms initiated by PEPE2 to evoke bladder cancer cell apoptosis. We found eleven down-regulated and eight up-regulated proteins in PEPE2-treated T24 cells. Our results implied that these PEPE2-dysregulated proteins belong to cell apoptosis, cell proliferation, death receptor signaling, JAK/STAT signaling, the PPAR pathway, the PPARα/RXR α pathway, Rho family GTPase signaling, and RhoGDI signaling. In addition, HSP90 and PTP1B proteins, associated with apoptosis, were de-regulated in xenografted bladder tumors in nude mice fed with an ethyl acetate layer of ethanol extract. The findings above implied that pomegranate might be a potential chemopreventive resource for UBUC carcinogenesis.
Keyphrases
- cell proliferation
- oxidative stress
- tandem mass spectrometry
- mass spectrometry
- liquid chromatography
- transcription factor
- ionic liquid
- high performance liquid chromatography
- spinal cord injury
- endoplasmic reticulum stress
- randomized controlled trial
- gas chromatography
- insulin resistance
- cell cycle arrest
- cell death
- high fat diet induced
- simultaneous determination
- body mass index
- anti inflammatory
- label free
- type diabetes
- ultra high performance liquid chromatography
- pi k akt
- fatty acid
- ms ms
- risk assessment
- heat shock protein
- smooth muscle
- human health
- signaling pathway
- high resolution mass spectrometry
- single molecule
- protein kinase