Blueberries contain numerous chemopreventive compounds, among them pterostilbene, resveratrol, and various anthocyanins (delphinidin, cyanidin, malvidin, peonidin, and petunidin). Pterostilbene has been shown to have powerful chemopreventive activities against breast cancer. p53 is a tumor suppressor gene that is often mutated in cancer.
Now a new study has reported that pterostilbene can reduce expression of mutant p53 in triple negative (ER-/PR-/HER2-) and hormone receptor positive (ER+/PR+) cells, thereby inhibiting the development and progression of breast cancer.
Pterostilbene and breast cancer
Pterostilbene, a bioavailable stilbenoid found primarily in blueberries and red grapes, is chemically similar to resveratrol but does not have identical properties. In fact, pterostilbene appears to have somewhat more diverse and powerful anti-cancer effects than resveratrol. For example, pterostilbene showed significantly more potent activity than resveratrol in suppressing brain metastasis in one study.
Pterostilbene has been shown to induce dose-dependent reductions in proliferation of hormone receptor positive, HER2/neu overexpressing (HER2+) and triple negative breast cancer cells without harming normal breast cells. Pterostilbene administered orally also has been shown to significantly suppress mammary tumor growth and metastasis in mouse models of triple negative breast cancer.
Pterostilbene also has been found to inhibit the formation of breast cancer stem cells and reduce their metastatic activities. The combination of resveratrol and pterostilbene was shown in one study to reactivate estrogen receptor (ER) expression in triple negative breast cancer cells, thereby reducing their aggressiveness. In addition, pterostilbene has been shown to have additive effects when combined with tamoxifen in estrogen receptor positive (ER+) breast cancer cells. Pterostilbene has also been shown to significantly increase the cytotoxic effects of Taxol (paclitaxel).
Finally, pterostilbene has been shown to reduce obesity-related breast cancer cell growth and proliferation.
p53 and breast cancer
p53 is a protein encoded by the tumor suppressor gene, p53. Normally, activation of the p53 gene results either in cell death or DNA repair, thereby preventing the progression of cells with incorrect numbers of chromosomes toward cancer. However, as noted above, the p53 gene often is mutated in cancer. Such mutations don't just disrupt the normal functioning of p53, they often also endow p53 with new functions that promote, instead of inhibit, cancer formation, proliferation and invasion. In that case, overexpression of the mutant p53 protein can enhance cancer development and decreased expression could inhibit it.
Latest research finds pterostilbene inhibits mutant p53
The study referenced above was designed to investigate the impact of pterostilbene on breast cancer cell lines with mutant p53. To conduct the study, the authors used MDA-MB-231 triple negative and T-47D hormone receptor positive (ER+/PR+/HER2-) breast cancer cells with mutant p53. Treatment with various concentrations of pterostilbene was found to significantly reduce the viability and proliferative activity of both cell types. In addition, the morphological characteristics (shape and structure) of both cell types were modified by pterostilbene treatment.
These cellular changes were accompanied by reduced expression of mutant p53 in both breast cancer cell lines. Other favorable changes in oncogene (cyclin D1, mTOR, and β-catenin) expression in both cell lines were also observed under various pterostilbene concentrations. The authors conclude that downregulation of protein expression of mutant p53 and other oncogenes was increased after triple negative and T-47D cell lines with mutant p53 were treated with pterostilbene. These results raise the possibility that pterostilbene might have promise as a natural therapeutic agent against the development and the progression of breast cancer, according to the authors.