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Suppression of urinary bladder urothelial carcinoma cell by the ethanol extract of pomegranate fruit through cell cycle arrest and apoptosis
- Source :
- BMC Complementary and Alternative Medicine
- Publisher :
- Springer Nature
-
Abstract
- Background Pomegranate possesses many medicinal properties such as antioxidant, anti-inflammation and antitumor. It has been extensively used as a folk medicine by many cultures. Pomegranate fruit has been shown to have the inhibitory efficacy against prostate cancer and lung cancer in vitro and in vivo. It can be exploited in chemoprevention and chemotherapy of prostate cancer. In this study we examined the anti-cancer efficacy of pomegranate fruit grown in Taiwan against urinary bladder urothelial carcinoma (UBUC) and its mechanism of action. Methods Edible portion of Taiwanese pomegranate was extracted using ethanol and the anti-cancer effectiveness of ethanol extract was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry and western immunoblotting were exploited to uncover the molecular pathways underlying anti-UBUC activity of Taiwanese pomegranate ethanol extract. Results This study demonstrated that Taiwanese pomegranate fruit ethanol extract (PEE) could effectively restrict the proliferation of UBUC T24 and J82 cells. Cell cycle analyses indicated that the S phase arrest induced by PEE treatment might be caused by an increase in cyclin A protein level and a decrease in the expression of cyclin-dependent kinase 1. The results of western immunoblotting demonstrated that PEE treatment could not only evoke the activation of pro-caspase-3, -8,-9 but also increase Bax/Bcl-2 ratio in T24 cells. The above observations implicated that PEE administration might trigger the apoptosis in T24 cells through death receptor signaling and mitochondrial damage pathway. Besides we found that PEE exposure to T24 cells could provoke intensive activation of procaspase-12 and enhance the expressions of CHOP and Bip, endoplasmic reticulum (ER) stress marker, suggesting that ER stress might be the cardinal apoptotic mechanism of PEE-induced inhibition of bladder cancer cell. Conclusions The analytical results of this study help to provide insight into the molecular mechanism of induced bladder cancer cell apoptosis by pomegranate and to develop novel mechanism-based chemopreventive strategy for bladder cancer.
- Subjects :
- Pathology
medicine.medical_specialty
Cell cycle checkpoint
Cyclin A
Cell
Antineoplastic Agents
Apoptosis
Prostate cancer
Cell Line, Tumor
medicine
Humans
Cell Proliferation
Lythraceae
Bladder cancer
biology
Plant Extracts
business.industry
Cell growth
Carcinoma
Cell Cycle Checkpoints
General Medicine
Cell cycle
medicine.disease
medicine.anatomical_structure
Urinary Bladder Neoplasms
Complementary and alternative medicine
Fruit
Cancer research
biology.protein
business
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 14726882
- Volume :
- 13
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- BMC Complementary and Alternative Medicine
- Accession number :
- edsair.doi.dedup.....377bffd2bb6f7e719fa231d756fe95be
- Full Text :
- https://doi.org/10.1186/1472-6882-13-364