We previously demonstrated that hormone treatments which stimulate female-directed singing increased levels and turnover of dopamine (DA) in brain areas controlling the motor patterning of song. To help determine how DA affects singing, we quantified the effects of treating adult male finches with the D 1 /D 2 receptor antagonist cis-flupenthixol. Adult males were given subcutaneous silastic implants of androgen, in case drug treatment interfered with androgen secretion. One week later, they were tested with females. Males were divided into three groups matched for levels of courtship singing. Males were then subcutaneously implanted with osmotic minipumps containing either saline, a low, or a high dose of cis-flupenthixol. Each male was tested with a different female 5 and 10 days after implantation to determine how this D 1 /D 2 receptor antagonist affected behavior. Both drug doses affected female-directed singing 5 days after initiation of treatment. High-dose males sang to females significantly less often than males in the other two groups. Low-dose males showed fewer high-intensity courtship displays in which males dance towards females as they sing. These effects on courtship singing were not seen at day 10, though other behavioral effects were seen at this time. Male beak wipes, rocks, following females and female withdrawals from males were also affected by drug treatment. General activity in the home cage was decreased by day 11. These data demonstrate that singing and several other female-directed behaviors are sensitive to perturbations in DA receptor function.

Every year, approximately half a million people die due to breast cancer (BC), comprising 16% of the incidence of all cancer occurrences in females. It is the most prevalent invasive cancer among women around the world. In several studies, researchers have suggested the presence of certain chemokines associated with cancer. The chemokine receptor CXCR4, a G‐protein coupled receptor, has a role in trafficking, cell activation, and differentiation in non‐malignant. It has been shown that CXCR4 is overexpressed in cancerous tissues compared to non‐malignant cells. This overexpression has led to an increase in proliferation, migration, and angiogenesis of malignant cells. Tissues with higher expression of the CXCR4 specific ligand CXCL12, are more likely to metastasis to tissue expressing CXCR4. These target tissues include lungs, bone marrow, and lymph nodes. Due to the impact of this disease, there is a need of developing new therapies or adjuvants to target BC. For example, resveratrol is a natural product and a polyphenol derived from grapes, wine, and nuts, among others. Recent studies found that it plays a role in apoptosis, inflammation, and neovascularization. We hypothesized that resveratrol will decrease the expression of CXCR4 in a dose and time‐dependent manner, leading to a decrease in the migration and invasion cellular processes. Using western blot analysis of HS578T (Human Breast Carcinoma) compared with CCD1074Sk (Non‐malignant Human Breast Tissue) cell lines we studied the effects of resveratrol at the CXCR4 protein level and invasion markers involved in metastatic processes. Migration and invasion were assessed using a wound healing assay and matrigel invasion assay, respectively. The preliminary data shows that as the concentration (25, 50, 100, 200μM) increases the cell migration and invasion decreases compared to our control vehicle (EtOH). In addition, we observed a decrease in the expression of pro‐migration and invasion proteins such as N‐cadherin and Cathepsin‐b. This study suggests an effect of resveratrol in cell migration and invasion leading to a decrease of the in‐vitro cell metastatic potential. Currently we are evaluating CXCR4 at the protein expression level to complete our data.Support or Funding InformationThis work was supported by UPR PRISE Program NIH‐NIGMS #2R25GM096955This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The cellular and molecular environment of normal cells from breast cancer patients are particulary understood. Chemokines and their receptors have roles in cellular proliferation, metastasis, and angiogenesis. Specifically, CXCR4, a G‐protein coupled receptor is expressed in high levels in breast neoplastic tissues and in low levels in normal breast tissue. CXCR4 expression may induce proliferation, migration, invasion and angiogenesis. Recent studies have identify resveratrol (a natural polyphenol) to play a role on inflammation, apoptosis, and neovascularization. Due to limited scientific literature on the effects of resveratrol on CXCR4, the biological process in which both coincide, (inflammation, apoptosis, and neovascularization), and the potential use of resveratrol, as a therapeutic agent in cancer, we studied the effect of this polyphenol on CXCR4. In addition, we explored the effects on the apoptosis mediator Bax. We hypothesized that resveratrol increases the expression of CXCR4 in normal cells from a breast cancer patient. We determined the effects of resveratrol at concentrations of 25, 50, 100, 200 μM after 24 hours of treatment in the protein levels of CXCR4 and Bax‐2 by western blot using CCD1097 a fibroblastic cell line, derived from normal skin from the breast of a patient undergoing biopsy of a grade III infiltrating ductal carcinoma. Our preliminary results indicate that higher doses increased expression of CXCR4 in a dose‐dependent compared to control vehicle treated cells. Similarly, Bax expression increased in all treated cells but in a non‐dependent dose manner. These results may suggest that resveratrol have an effect on CXCR4 protein levels, leading to an increase in proliferation in normal cells from cancer patients. As reported, at lower doses resveratrol may have antiapoptotic effects and at higher doses may induce apoptosis. Resveratrol may prompt for clearance of cancer cells using different pathways but additional experiments will be necessary to identify the exact mechanism of action. Additional experiments are underway to identify the proliferative effects of resveratrol including apoptosis (caspases) and inflammation (TNF‐α and SOD‐2).Support or Funding InformationThis work was supported by UPR PRISE Program NIH Grant #R25GM096955.