Anticancer Activity in Honeybee Propolis: Functional Insights to the Role of Caffeic Acid Phenethyl Ester and Its Complex With γ-Cyclodextrin

Besides honey, honeybees make a sticky substance (called propolis/bee glue) by mixing saliva with poplar tree resin and other botanical sources. It is known to be rich in bioactivities of which the anticancer activity is most studied. Caffeic acid phenethyl ester (CAPE) is a key anticancer component...

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Main Authors: Yoshiyuki Ishida PhD, Ran Gao PhD, Navjot Shah PhD, Priyanshu Bhargava MS, Takahiro Furune PhD, Sunil C. Kaul PhD, Keiji Terao PhD, Renu Wadhwa PhD
Format: Article
Language:English
Published: SAGE Publishing 2018-09-01
Series:Integrative Cancer Therapies
Online Access:https://doi.org/10.1177/1534735417753545
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author Yoshiyuki Ishida PhD
Ran Gao PhD
Navjot Shah PhD
Priyanshu Bhargava MS
Takahiro Furune PhD
Sunil C. Kaul PhD
Keiji Terao PhD
Renu Wadhwa PhD
author_facet Yoshiyuki Ishida PhD
Ran Gao PhD
Navjot Shah PhD
Priyanshu Bhargava MS
Takahiro Furune PhD
Sunil C. Kaul PhD
Keiji Terao PhD
Renu Wadhwa PhD
author_sort Yoshiyuki Ishida PhD
collection DOAJ
description Besides honey, honeybees make a sticky substance (called propolis/bee glue) by mixing saliva with poplar tree resin and other botanical sources. It is known to be rich in bioactivities of which the anticancer activity is most studied. Caffeic acid phenethyl ester (CAPE) is a key anticancer component in New Zealand propolis. We have earlier investigated the molecular mechanism of anticancer activity in CAPE and reported that it activates DNA damage signaling in cancer cells. CAPE-induced growth arrest of cells was mediated by downregulation of mortalin and activation of p53 tumor suppressor protein. When antitumor and antimetastasis activities of CAPE were examined in vitro and in vivo, we failed to find significant activities, which was contrary to our expectations. On careful examination, it was revealed that CAPE is unstable and rather gets easily degraded into caffeic acid by secreted esterases. Interestingly, when CAPE was complexed with γ-cyclodextrin (γCD) the activities were significantly enhanced. In the present study, we report that the CAPE-γCD complex with higher cytotoxicity to a wide range of cancer cells is stable in acidic milieu and therefore recommended as an anticancer amalgam. We also report a method for preparation of stable and less-pungent powder of propolis that could be conveniently used for health and therapeutic benefits.
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spelling doaj.art-c51e991565bc4ce4b1b4ccde6a91b4d72022-12-21T20:08:37ZengSAGE PublishingIntegrative Cancer Therapies1552-695X2018-09-011710.1177/1534735417753545Anticancer Activity in Honeybee Propolis: Functional Insights to the Role of Caffeic Acid Phenethyl Ester and Its Complex With γ-CyclodextrinYoshiyuki Ishida PhD0Ran Gao PhD1Navjot Shah PhD2Priyanshu Bhargava MS3Takahiro Furune PhD4Sunil C. Kaul PhD5Keiji Terao PhD6Renu Wadhwa PhD7CycloChem Co, Ltd, Chuo-ku, Kobe, JapanPeking Union Medical College, Beijing, ChinaNational Institute of Advanced Industrial Science & Technology, Tsukuba, JapanUniversity of Tsukuba, Ibaraki, JapanCycloChem Co, Ltd, Chuo-ku, Kobe, JapanNational Institute of Advanced Industrial Science & Technology, Tsukuba, JapanCycloChem Co, Ltd, Chuo-ku, Kobe, JapanNational Institute of Advanced Industrial Science & Technology, Tsukuba, JapanBesides honey, honeybees make a sticky substance (called propolis/bee glue) by mixing saliva with poplar tree resin and other botanical sources. It is known to be rich in bioactivities of which the anticancer activity is most studied. Caffeic acid phenethyl ester (CAPE) is a key anticancer component in New Zealand propolis. We have earlier investigated the molecular mechanism of anticancer activity in CAPE and reported that it activates DNA damage signaling in cancer cells. CAPE-induced growth arrest of cells was mediated by downregulation of mortalin and activation of p53 tumor suppressor protein. When antitumor and antimetastasis activities of CAPE were examined in vitro and in vivo, we failed to find significant activities, which was contrary to our expectations. On careful examination, it was revealed that CAPE is unstable and rather gets easily degraded into caffeic acid by secreted esterases. Interestingly, when CAPE was complexed with γ-cyclodextrin (γCD) the activities were significantly enhanced. In the present study, we report that the CAPE-γCD complex with higher cytotoxicity to a wide range of cancer cells is stable in acidic milieu and therefore recommended as an anticancer amalgam. We also report a method for preparation of stable and less-pungent powder of propolis that could be conveniently used for health and therapeutic benefits.https://doi.org/10.1177/1534735417753545
spellingShingle Yoshiyuki Ishida PhD
Ran Gao PhD
Navjot Shah PhD
Priyanshu Bhargava MS
Takahiro Furune PhD
Sunil C. Kaul PhD
Keiji Terao PhD
Renu Wadhwa PhD
Anticancer Activity in Honeybee Propolis: Functional Insights to the Role of Caffeic Acid Phenethyl Ester and Its Complex With γ-Cyclodextrin
Integrative Cancer Therapies
title Anticancer Activity in Honeybee Propolis: Functional Insights to the Role of Caffeic Acid Phenethyl Ester and Its Complex With γ-Cyclodextrin
title_full Anticancer Activity in Honeybee Propolis: Functional Insights to the Role of Caffeic Acid Phenethyl Ester and Its Complex With γ-Cyclodextrin
title_fullStr Anticancer Activity in Honeybee Propolis: Functional Insights to the Role of Caffeic Acid Phenethyl Ester and Its Complex With γ-Cyclodextrin
title_full_unstemmed Anticancer Activity in Honeybee Propolis: Functional Insights to the Role of Caffeic Acid Phenethyl Ester and Its Complex With γ-Cyclodextrin
title_short Anticancer Activity in Honeybee Propolis: Functional Insights to the Role of Caffeic Acid Phenethyl Ester and Its Complex With γ-Cyclodextrin
title_sort anticancer activity in honeybee propolis functional insights to the role of caffeic acid phenethyl ester and its complex with γ cyclodextrin
url https://doi.org/10.1177/1534735417753545
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