Abstract
Alternative remedies for cancer treatment is a multi-billion dollar industry. In particular, breast cancer (BC) patients use alternative and natural remedies more frequently than patients with other malignancies. Propolis is an example of a honeybee-produced naturopathic formulation, contents of which differ by geographic location. It is readily available, affordable, and in use safely since ancient times globally. Caffeic acid phenethyl ester (CAPE) is a major active component in propolis and is thought to be responsible for its varied properties, including antibacterial, antiviral, antifungal, antioxidant, anti-inflammatory and anticancer. CAPE is effective in many models of human cancer, including BC as we have previously shown. CAPE affects genes associated with tumor cell growth and survival, angiogenesis and chemoresistance. We demonstrate that these are related in part to CAPE's role as a histone deacetylase inhibitor, a class of drugs designated as epigenetic agents that modulate the activities of oncogenes and tumor suppressor genes. CAPE and propolis, cause an accumulation of acetylated histone proteins in MCF-7 (ER+) and MDA-MB-231 (ER-/PR-/Her2-) cells with associated decreases in ER and PR in MCF-7 cells, and upregulation of ER and decrease in EGFR in MDA-231 cells. In addition, these products reduced activated phosphorylated Her2 protein in SKBR3 (Her2 +) cells. Interestingly, propolis, when normalized for CAPE content, appears to be more potent than CAPE alone similarly to the greater effects of complete foods than isolated components. These data provide a potential mechanistic basis for one of the oldest naturopathic agents used in medicine and cancer treatment.
Highlights
The use of alternative therapies for the treatment of cancer is rapidly growing in popularity in the U.S, amounting to a multi-billion dollar industry according to the Nutritional business journal (NBJ) Integrative Medicine Report in 2009
We show that the cytotoxic effects of Caffeic acid phenethyl ester (CAPE) are intact in the natural product, propolis in the different breast cancer cell lines and we show for the first time the inhibitory effects on the Her2 over expressing breast cancer cell line SKBR3
We show that CAPE and propolis are cytotoxic to Her2 over expressing breast cancer cells and to other histone deacetylases inhibitors (HDACi) causes a decrease in phoshorylated Her2 in the Her2 over expressing cell line SKBR3 (Figure 6)
Summary
The use of alternative therapies for the treatment of cancer is rapidly growing in popularity in the U.S, amounting to a multi-billion dollar industry according to the Nutritional business journal (NBJ) Integrative Medicine Report in 2009. Up to 80% of cancer patients admit to using complementary or alternative medicine [1]. Cancer patients use these supplements despite recommendations not to do so by their oncologists. Breast cancer (BC) patients, in particular, favor the use of alternative and natural remedies, with as many as 63%-83% of BC patients admitting to the use of at least one type of alternative medicine, and 25%-63% admitting to the routine self-administration of herbal and vitamin remedies [2,3,4,5], despite medical advice. Caffeic acid phenethyl ester (CAPE) is one of the main medicinal components of the natural product, propolis produced by American and European honeybees. Literature going back to ancient times, reveal that Propolis has been used as a natural remedy. Egyptians knew very well the antiputrefactive properties of propolis and used it to embalm cadavers
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