MedWire News: In vitro and in vivo study results show that the polyphenols found in red wine and green tea halt the growth of prostate cancer cells by disrupting a vital cell signaling pathway.
Olivier Cuvillier (Centre National de la Recherche Scientifique, Toulouse, France) and colleagues used prostate cancer cell lines and mouse models to demonstrate that treatment with these dietary agents results in inhibition of the sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) pathway.
“SphK1 activity is crucial for the growth and survival of prostate cancer cells, because its inhibition through pharmacological or silencing approaches induces apoptosis,” the team explains in the FASEB journal.
Cuvillier et al evaluated the role of SphK1 signaling in response to epigallocatechin gallate (EGCg), resveratrol, a mixture of polyphenols (PPE) from green tea, and grapevine extract (vineatrol) in PC-3 prostate cancer cells and genetically altered mice that developed PC-3 cell prostate cancer.
Their results show that EGCg and PPE inhibited PC-3 cell growth with a half maximal inhibitory concentration (IC50) value at 48 hours of approximately 75 µm and 50 µg/ml, respectively. The respective values for resveratrol and vineatrol were approximately 10 and 20 µg/ml at 48 hours.
At these same IC50 value concentrations, the researchers also observed more than 50% inhibition of SphK1 activity and expression occurring within 90 to 180 minutes of treatment. At 72 hours after treatment, SphK1 activity had decreased by 75% or more.
The researchers note that the up-regulation of SphK1 resulted in reduced effects of red wine and green tea polyphenols.
“SphK1-overexpressing PC-3 cells were remarkably resistant to cell death induced by resveratrol, vineatrol, EGCg, and PPE,” they write.
Using the PC-3 mice, the team showed that after 2 weeks of treatment with resveratrol, vineatrol, or EGCg, the average prostate tumor volume and intratumoral SphK1 activity was significantly reduced compared with no treatment.
Importantly, note Cuvillier and team, both an EGCg and PPE diet were associated with a significant reduction in the occurrence and number of metastases in the mice.
Furthermore, tumor size was significantly 50–60% smaller in PC-3-infected animals treated with EGCg or resveratrol, compared with those who had forced, up-regulated SphK1 (and polyphenol treatment), at 20–25%, which further illustrates the resistance of PC-3 cell death in the presence of SphK1.
In addition to demonstrating that the “pro-survival, anti-apoptotic SphK1/SIP pathway represents a target of dietary green tea and wine polyphenols in cancer,” the researchers believe their findings may provide a rationale for chemoprevention in other cancer models.
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