Susan G Komen  
I've Been Diagnosed With Breast Cancer Someone I Know Was Diagnosed Share Your Story Join Us And Stay Informed Donate To End Breast Cancer
    Home > Research & Grants > Grants Program > Research Grants > Research Grants Awarded > Abstract

    Research Grants Awarded

    Caffeic Acid Phenethyl Ester (CAPE, Product of Propolis) as Potential Preventive and/or Therapeutic Agent for Breast Cancer

    Study Section:
    RISK and Prevention, Epidemiology

    Scientific Abstract:
    Background: Caffeic acid phenethyl ester ( CAPE ), an antiinflammatory and anti­oxidant component in the propolis of honeybee hives, is credited for its medicinal properties. Since breast cancer (BCa) therapies cause serious side effects, an agent inhibiting human BCa growth at nontoxic doses could be useful in treating patients. We propose to carry out preliminary studies to prove that CAPE possesses such properties. Objective/Hypothesis: To test in a nude mouse xenograft model our hypothesis that CAPE can act as preventive, therapeutic, or as adjuvant to a standard BCa therapy. Specific Aims: ( 1): Establish the mechanism of CAPE ’s toxicity to BCa cells. ( 2): E valuate CAPE ’s influence on growth of estrogen receptor (ER)- a positive ( + ) & negative (-) BCa cells in nude mice. ( 3): Compare CAPE ’s efficacy in vivo with those of tamoxifen (Tam) or paclitaxel, or when applied together with them. Study Design: (1): Since ER- a status has a pronounced effect on BCa progression, MCF-7(+) & MDA-MB-231(-) (MDA-231), will be used and their in vitro responses to CAPE compared to those of control cells [MCF-12A(+) & MCF-10A(-)]. CAPE ’s effects also will be compared to those of Tam or paclitaxel, agents used for prevention or treatment of BCa patients. Cell cycle arrest, cyclins, cdk, and apoptosis will be determined by flow cytometry, Western blot, and DNA fragmentation. (2): BCa cells will be implanted in the flanks of 10 groups of nude mice (5 groups/BCa cell line). Group 1 will be on a regular diet, groups 2&3 will start on 0.05% or 0.15% CAPE (nontoxic doses) diet one week before cell injection , groups 4&5 will start CAPE diets after tumors are established, and 2 groups (no cells) will be on CAPE diets. Tumor volume and histological evaluation will be determined. (3): Similar experiments will be performed using paclitaxel (MDA-231 cells) or tamoxifen (MCF-7 cells) alone, or in conjunction with CAPE diet. Potential Outcomes & Benefits of the Research: We found that CAPE significantly decreases in vitro growth of both BCa cell lines. Hence, we expect that CAPE will suppress in vivo growth of tumor cells and inhibit growth of establish tumors. Such results would indicate that CAPE acts as a preventive agent and has therapeutic potential, respectively. CAPE also might be efficient when used in combination with paclitaxel or Tam. CAPE ’s effectiveness against these BCa cells either alone or as an adjuvant to a therapeutic agent, may lead to clinical trials.

    Lay Abstract:
    Background: Caffeic acid phenethyl ester ( CAPE ), an antiinflammatory and anti­oxidant component in the propolis (a wax-like substance) of honeybee hives, is credited for its medicinal properties. Since breast cancer (BCa) therapies cause serious side effects, an agent nontoxic to normal cells that inhibits BCa could be useful in treating patients. We propose to carry out preliminary studies to prove that CAPE possesses such properties. Objective/Hypothesis: To test whether CAPE can act as preventive or therapeutic agent, or together with standard therapy using a mouse model. Our hypothesis is that CAPE ’s toxicity is due to stopping BCa cell growth and inducing cell death. Specific Aims: ( 1): Establish whether CAPE decreases human BCa cell growth and by what mechanism. ( 2): E valuate CAPE ’s influence on growth of BCa cells in mice that differ in estrogen receptor (ER)- a status. CAPE will be provided in a diet. ( 3): Compare CAPE ’s efficacy with those of tamoxifen (Tam) or paclitaxel, standard therapeutic agents, or when CAPE is applied with either of them. Study Design: (1): Since ER- a status has a pronounced effect on BCa progression, BCa cell lines differing in ER- a status will be tested for their responses to CAPE and will be compared to responses of control cells also differing in ER- a status. CAPE ’s effects on BCa cell growth also will be compared to those of Tam or paclitaxel. (2): BCa cells will be implanted in the flanks of 10 groups of immunosuppressed mice (5 groups/BCa cell line). Group 1 will be fed regular diet, groups 2&3 will start on the 0.05% or 0.15% CAPE (nontoxic doses) diets a week before BCa cell injection , groups 4&5 will start CAPE diets after tumors develop , and two groups will be on CAPE diets without cells. Size of tumors and pathological evaluation will be determined. (3): Similar experiments will be carried out using paclitaxel or Tam alone, or together with a CAPE diet. Potential Outcomes & Benefits of the Research: We found that CAPE significantly decreases growth of ER- a positive and negative BCa cell lines. Hence, we expect that CAPE will suppress tumor cell growth in mice and inhibit growth of establish tumors. Such results would indicate that CAPE acts as a preventive agent and has therapeutic potential. CAPE also might be efficient when used in combination with paclitaxel or Tam. CAPE’s effectiveness against BCa cells when applied alone or together with a therapeutic agent, may lead to clinical trials.