Abstract
Metastasis is a multifactorial condition that complicates cancer treatment options and widens the target of treatment. Matrix mettalopriteinases (MMPs) of the extracellular matrix (ECM) are involved in metastasis, thus they present as potential targets in halting cancer metastasis. The study was undertaken to investigate the influence of naringenin, a naturally occurring flavonoid on the metastasis of human prostate cancer cells (PC-3 and DU145). Naringenin was observed to be effective in reducing the viability and migratory percentage of PC-3 and DU145 cells. Naringenin significantly reduced the expression and activities of the chief MMPs (MMP-2 and MMP-9) as assessed by western blotting, real-time PCR and gelatin zymography analysis. The influence of naringenin on extracellular signal-regulated kinase (ERK) -ERK1/2 was analysed by western blotting. The results indicated that naringenin was able to effectively inhibit ERK1/2. Naringenin exposure also significantly suppressed the levels of reactive oxygen species (ROS). Naringenin thus stands as an effective chemotherapeutic agent for prostate cancer treatment that could be further explored.
Highlights
Prostate cancer has been reported as the most common cancer in men accounting as the second most common cancer globally (Jemal et al, 2011)
PC-3 and DU145 prostate cancer cells were exposed to various concentrations of naringenin (10 or 50 μM)
The expression of Matrix mettalopriteinases (MMPs)-2 mRNA dropped 36.1% in PC-3 cells and 31.1% in DU145 cells as against control. These findings suggest that down-regulation of MMP-2 and -9 enzyme activities and expressions might be involved in the inhibition of invasion and migration of the prostate cancer cells
Summary
Prostate cancer has been reported as the most common cancer in men accounting as the second most common cancer globally (Jemal et al, 2011). Matrix metalloproteinases (MMPs), a family of endopeptidases majorly are involved in tumour cell migration, tissue invasion and metastasis (Itoh and Nagase, 2002). Over expression of MMPs has been reported as cancer progresses (Kilian et al, 2006; Mizutani et al, 2000; Gullu et al, 2000). The activation of MMP-2 and -9 has been reported to be associated with increasing tumour metastasis (Mook et al, 2004). Inhibition of the activities of the MMP enzymes could be contemplated as targets for preventing cancer metastasis (Guruvayoorappan et al, 2008; Zucker and Vacirca, 2004). The present study was undertaken to investigate the effect of naringenin on metastasis of prostate cancer cells by evaluating the expression of MMPs-2/-9 and ERK1/2
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