Resveratrol, a polyphenol found primarily in grapes, berries, and nuts, has been found to have powerful anti-cancer properties without being toxic to normal cells. While resveratrol is a phytoestrogen, it exerts chemopreventive effects through multiple pathways — it can inhibit the growth of both hormone receptor positive (ER+/PR+) and hormone receptor negative (ER-/PR-) breast cancer cells. Resveratrol can prevent silencing of the BRCA1 gene, a gene that protects against breast cancer through its role in repairing DNA damage.
Resveratrol has also been shown to increase the effectiveness of a variety of breast cancer treatments. For example, resveratrol has been shown to potentiate the effects of several chemotherapy drugs (Adriamycin, Alkeran, cisplatin, Taxol and Taxotere), the epidermal growth factor receptor (EGFR) inhibitor Iressa, tamoxifen, and radiation treatment. Now a new study has helped explain the mechanism of action by which resveratrol enhances the treatment effects of Taxol (paclitaxel) in estrogen receptor positive (ER+) breast cancer cells.
Resveratrol supplements and red wine are not good choices
We urge those undergoing chemotherapy to consume foods such as red grapes, blueberries and cranberries to obtain resveratrol rather than consuming it in supplement form. Safe and effective dosages of resveratrol have not been established. Taking it in concentrated form separate from the other nutrients found in foods could have unintended adverse effects. For example, one study reported that resveratrol alone promoted mammary tumor growth and metastasis in a mouse model of estrogen receptor negative (ER-) breast cancer whereas it inhibited it in combination with other grape polyphenols. Another study reported that supplementation with resveratrol plus zinc in a rat model of breast cancer significantly increased the rate of development and number of carcinogen-induced mammary tumors.
The best food sources of resveratrol for breast cancer patients and survivors are red grapes and grape juice, blueberries and cranberries. Other potentially beneficial foods with significant levels of resveratrol include strawberries and pistachio nuts. Blackberries and raspberries also contain some resveratrol. While red wine is an abundant source of resveratrol, its alcohol content makes it on balance harmful.
Latest research show how resveratrol potentiates Taxol in ER+ cells
While neuroglobin is an oxygen binding protein expressed primarily in the nervous system, it also has a role in breast cancer estrogen signaling. A signaling pathway consists of a set of molecules that participate in a cascade of chemical reactions that together control cellular processes such as cell division or programmed cell death (apoptosis). In some cases, such as estrogen signaling pathways, a pathway can be initiated when a molecule, such as a hormone, attaches to a receptor on the cell membrane. Cellular levels of neuroglobin, which has a role in preventing apoptosis, are increased (upregulated) by the estrogen 17β‐estradiol (E2). As such, neuroglobin is part of an E2/estrogen receptor alpha (ERα) pathway which serves to prevent cancer cell death in presence of stressors such as chemotherapy drugs.
In the study, the authors investigated the possibility that resveratrol could increase the susceptibility of breast cancer cells to Taxol by influencing the E2/ERα/neuroglobin pathway. Resveratrol was found to reduce neuroglobin levels in ERα‐positive (MCF‐7 and T47D), but not in ERα‐negative (MDA‐MB 231) or in ERα and ERβ positive (SK‐N‐BE) breast cancer cells. Resveratrol reduced neuroglobin levels by interfering with both E2/ERα‐induced neuroglobin upregulation and E2‐induced ERα and protein kinase B (Akt) phosphorylation (which is involved in the induction of autophagy, another form of cell death). Although treatment with resveratrol did not appear to reduce breast cancer cell viability directly, it increased Taxol's proapoptotic effects. The authors note that the findings demonstrate for the first time how resveratrol impairs the E2/ERα/neuroglobin signaling pathway and increases ERα breast cancer cell susceptibility to a chemotherapeutic agent.