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Prostate Int. 2017 Jun;5(2):75-83. doi: 10.1016/j.prnil.2017.03.002. Epub 2017 Mar 16.

Withania somnifera targets interleukin-8 and cyclooxygenase-2 in human prostate cancer progression.

Author information

1
Department of Genetic Engineering, School of Biotechnology, Madurai Kamaraj University, Madurai, India.
2
Department of Pathology, Velammal Medical College Hospital & Research Institute, Madurai, India.
3
Department of Urology, Velammal Medical College Hospital & Research Institute, Madurai, India.

Abstract

BACKGROUND:

Prostate cancer (PC) is a common noncutaneous malignancy in men. The incidence of PC is increasing at an alarming rate across the globe. Progression of PC is associated with elevated levels of interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2) in malignant cells. Overexpression of these players is accompanied by chronic inflammation, increased angiogenesis, proliferation, migration, and inhibition of apoptosis. Moreover, their elevated circulating levels promote the disease progression from androgen-dependent to androgen-independent state. Thus, inhibiting the expression of IL-8 and COX-2 would be a promising target in the development of PC therapeutics. In this study, we investigated the inhibitory effects of Withania somnifera extract on highly metastatic, androgen-independent prostate cancer cell line (PC3). Additionally, we compared the real-time expression of IL-8 and COX-2 in prostate tissue samples.

MATERIALS AND METHODS:

The cell viability and cytotoxicity of W. somnifera extract in PC3 cells was quantified colorimetrically by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase leakage assay, respectively. Hematoxylin and eosin staining for histological examination, trypan blue, and acridine orange dyes to enumerate apoptotic and live cells, quantitative real-time polymerase chain reaction to determine the expression and flow cytometry to study the cell cycle analysis were used.

RESULTS:

We observed a significant decrease in the cell viability with a half-maximal inhibitory concentration (IC50) of 10 μg/mL. The expression levels of IL-8 and COX-2 in prostate tissue samples and in PC3 cells were predominantly high; however, the lowest dose of W. somnifera significantly inhibited the enhanced expression of IL-8 and COX-2 in PC3 cells in 24 hours. Furthermore, W. somnifera extract (10 μg/mL) irreversibly arrested the cell cycle in G2/M phase, which was evident from the rapid accumulation of PC3 cells significantly.

CONCLUSION:

Our results indicate that inherent metastatic and selective inhibitory potential of W. somnifera against PC. W. somnifera may be a good therapeutic agent in addition to the existing drugs for PC. Further studies with more prostate tissue samples are warranted.

KEYWORDS:

Androgen-independent cells; Cyclooxygenase-2; Interleukin-8; Prostatic adenocarcinoma; Withania somnifera

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