Apoptotic markers in a prostate cancer cell line: Effect of ellagic acid

Vanella,Luca; Di Giacomo,Claudia; Acquaviva,Rosaria; Barbagallo,Ignazio; Cardile,Venera; Kim,Dong  Hyun; Abraham,Nader   G.; Sorrenti,Valeria

doi:10.3892/or.2013.2757

Apoptotic markers in a prostate cancer cell line: Effect of ellagic acid

Authors:
- Luca Vanella
- Claudia Di Giacomo
- Rosaria Acquaviva
- Ignazio Barbagallo
- Venera Cardile
- Dong Hyun Kim
- Nader G. Abraham
- Valeria Sorrenti
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Affiliations: Department of Drug Science, Section of Biochemistry, University of Catania, I-95125 Catania, Italy, Department of Bio-Medical Sciences, Section of Physiology, University of Catania, I-95125 Catania, Italy, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA
Published online on: September 30, 2013 https://doi.org/10.3892/or.2013.2757
Pages: 2804-2810

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Abstract

Ellagic acid (EA) inhibits cell growth and induces apoptosis in cultured cells; however, the precise molecular mechanism involved in EA-induced apoptosis in prostate cancer cells is unknown. The aim of the present study was to delineate possible apoptotic pathway(s) involved in the EA-mediated chemotherapeutic effects in the LNCaP human prostatic cancer cell line. EA produced anti-proliferative effects through inhibition of rapamycin (mTOR) activation and a reduction in intracellular levels of β-catenin. Moreover, we demonstrated that EA induced apoptosis via downregulation of the anti-apoptotic proteins, silent information regulator 1 (SIRT1), human antigen R (HuR) and heme oxygenase-1 (HO-1). EA modulated the expression of apoptosis-inducing factor (AIF) resulting in a significant increase in reactive oxygen species (ROS) levels and the activation of caspase-3. Finally, we demonstrated that EA reduced both transforming growth factor-β (TGF-β) and interleukin-6 (IL-6) levels. EA treatment resulted in the increased expression of the tumor suppressor protein p21 and increased the percentage of apoptotic cells. In conclusion, the results suggest that EA treatment represents a new and highly effective strategy in reducing prostate cancer carcinogenesis.

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