Caffeic acid phenethyl ester [CAPE]

[pca2004]

New study [1].

"Caffeic acid phenethyl ester suppresses EGFR/FAK/Akt signaling, migration, and tumor growth of prostate cancer cells"

There have been 2 dozen CAPE papers these last 20 years. Ten of these specifically mention Akt inhibition.

CAPE is found in propolis, which bees use to seal gaps in the hive and protect the colony against infection. (Polis is Greek for "city" or colony.)

I used cheap propolis supplements before discovering that the CAPE content varies & there is often no CAPE at all. I have been using "Manuka Health Propolis Capsules 500Mg, 500 Count" from New Zealand. From the sales pitch: "Scientists have identified very high levels of bioactive compounds including Caffeic Acid Phenethyl Ester (CAPE) in Manuka Health's BIO New Zealand Propolis, for powerful immune support."

From the paper:

"Epidermal growth factor receptor (EGFR) is upregulated in prostate cancer (PCa). However, suppression of EGFR did not improve the patient outcome, possibly due to the activation of PI3K/Akt signaling in PCa. Compounds able to suppress both PI3K/Akt and EGFR signaling may be effective for treating advanced PCa."

"Wound healing assay, transwell migration assay and xenograft mice model were used to determine the effects of CAPE on migration and proliferation of PCa cells."

"CAPE treatment decreased the gene expression of HRAS, RAF1, AKT2, GSK3A, and EGF and the protein expression of phospho-EGFR (Y845, Y1069, Y1148, Y1173), phospho-FAK, Akt, and ERK1/2 in PCa cells.

"CAPE treatment inhibited the EGF-induced migration of PCa cells.

Combined treatment of CAPE with EGFR inhibitor gefitinib showed additive inhibition on migration and proliferation of PCa cells.

"Injection of CAPE (15 mg/kg/3 days) for 14 days suppressed the tumor growth of prostate xenografts in nude mice as well as suppressed the levels of Ki67, phospho-EGFR Y845, MMP-9, phospho-Akt S473, phospho-Akt T308, Ras, and Raf-1 in prostate xenografts."

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/372...

Phytomedicine. 2023 May 3;116:154860. doi: 10.1016/j.phymed.2023.154860.Online ahead of print.

Caffeic acid phenethyl ester suppresses EGFR/FAK/Akt signaling, migration, and tumor growth of prostate cancer cells

Jen-Chih Tseng 1, Bi-Juan Wang 2, Ya-Pei Wang 2, Ying-Yu Kuo 2, Jen-Kun Chen 3, Tzyh-Chyuan Hour 4, Li-Kuo Kuo 5, Po-Jen Hsiao 6, Chien-Chih Yeh 7, Cheng-Li Kao 8, Li-Jane Shih 9, Chih-Pin Chuu 10

PMID: 37201366 DOI: 10.1016/j.phymed.2023.154860

Abstract

Background: Epidermal growth factor receptor (EGFR) is upregulated in prostate cancer (PCa). However, suppression of EGFR did not improve the patient outcome, possibly due to the activation of PI3K/Akt signaling in PCa. Compounds able to suppress both PI3K/Akt and EGFR signaling may be effective for treating advanced PCa.

Purpose: We examined if caffeic acid phenethyl ester (CAPE) simultaneously suppresses the EGFR and Akt signaling, migration and tumor growth in PCa cells.

Methods: Wound healing assay, transwell migration assay and xenograft mice model were used to determine the effects of CAPE on migration and proliferation of PCa cells. Western blot, immunoprecipitation, and immunohistochemistry staining were performed to determine the effects of CAPE on EGFR and Akt signaling.

Results: CAPE treatment decreased the gene expression of HRAS, RAF1, AKT2, GSK3A, and EGF and the protein expression of phospho-EGFR (Y845, Y1069, Y1148, Y1173), phospho-FAK, Akt, and ERK1/2 in PCa cells. CAPE treatment inhibited the EGF-induced migration of PCa cells. Combined treatment of CAPE with EGFR inhibitor gefitinib showed additive inhibition on migration and proliferation of PCa cells. Injection of CAPE (15 mg/kg/3 days) for 14 days suppressed the tumor growth of prostate xenografts in nude mice as well as suppressed the levels of Ki67, phospho-EGFR Y845, MMP-9, phospho-Akt S473, phospho-Akt T308, Ras, and Raf-1 in prostate xenografts.

Conclusions: Our study suggested that CAPE can simultaneously suppress the EGFR and Akt signaling in PCa cells and is a potential therapeutic agent for advanced PCa.

Keywords: Akt; Caffeic acid phenethyl ester; Epidermal growth factor receptor; Fak; Metastasis; Prostate cancer.

Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.