Honeybee Propolis Extract Impedes Prostate Cancer Cell Growth

Cancer researchers have discovered the molecular mechanism that utilizes the honeybee propolis component caffeic acid phenethyl ester (CAPE) to arrest the growth of prostate cancer cells in culture and in mouse xenografts.

CAPE is a bioactive component derived from honeybee hive propolis. It has been shown to have antimitogenic, anticarcinogenic, and other beneficial medicinal properties. Many of its effects have been shown to be mediated through its inhibition of NF-kappaB signaling pathways. Notably, CAPE down-regulates the mdr-1 gene, considered responsible for the resistance of cancer cells to chemotherapeutic agents.

In the current study investigator at the University of Chicago (IL, USA) employed a systematic approach to uncover the long- and short- term effects of CAPE on the signaling networks in human prostate cancer cells.

They reported in the May 1, 2012, issue of the journal Cancer Prevention Research that dosages of CAPE dependently suppressed the proliferation in culture of the LNCaP, DU-145, and PC-3 lines of human prostate cancer cells. Furthermore, administration of CAPE significantly inhibited growth of LNCaP tumor xenografts in nude mice.

Working with LNCaP cells as a model system, the investigators examined the effect of CAPE on gene expression, protein signaling, and transcriptional regulatory networks using a novel series of micro-Western and PCR arrays. They found that CAPE acted through inhibition of Akt-related protein signaling networks. Akt, also known as protein kinase B (PKB), is a serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration. Overexpression of Akt-1 or c-Myc (v-myc myelocytomatosis viral oncogene homolog), a downstream target of Akt signaling, significantly blocked the antiproliferative effects of CAPE.

“If you feed CAPE to mice daily, their tumors will stop growing. After several weeks, if you stop the treatment, the tumors will begin to grow again at their original pace,” said senior author Dr. Richard B. Jones, assistant professor of genomics and systems biology at the University of Chicago. “So it does not kill the cancer, but it basically will indefinitely stop prostate cancer proliferation.”

“It appears that CAPE basically stops the ability of prostate cancer cells to sense that there is nutrition available. They stop all of the molecular signatures that would suggest that nutrition exists, and the cells no longer have that proliferative response to nutrition,” said Dr. Jones. “A typical problem in bringing some of these herbal remedies into the clinic is that nobody knows how they act, nobody knows the mechanism, and therefore researchers are typically very hesitant to add them to any pharmaceutical treatment strategy. Now we will actually be able to systematically demonstrate the parts of cell physiology that are affected by these compounds.”

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