Abstract
Withaferin A (Wi-A) and Caffeic Acid Phenethyl Ester (CAPE) are the bioactive ingredients of Ashwagandha (Withania somnifera) and propolis, respectively. Both of these natural compounds have been shown to possess anticancer activity. In the present study, we recruited a low dose of each of these compounds and developed a combination that exhibited remarkably potent anti-migratory and anti-angiogenic activities. Extensive molecular analyses including a cDNA array and expression analyses of the specific gene targets demonstrated that such activities are mediated through their effect on cell adhesion/tight junction proteins (Claudins, E-cadherin), inhibition of canonical Wnt/β-catenin signaling pathways and the consequent downregulation of EMT-signaling proteins (Vimentin, MMPs, VEGF and VEGFR) that play a critical role in cancer metastasis. The data supported that this novel combination of Wi-A and CAPE (Wi-ACAPE, containing 0.5 µM of Wi-A and 10 µM of CAPE) may be recruited for the treatment of metastatic and aggressive cancers and, hence, warrant further evaluation by recruiting a variety of experimental and clinical metastatic models.
Original language | English |
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Article number | 787 |
Number of pages | 23 |
Journal | Cancers |
Volume | 14 |
Issue number | 3 |
DOIs | |
Publication status | Published - 3 Feb 2022 |
Externally published | Yes |
Bibliographical note
Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Funding
Funders | Funder number |
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National Institute of Advanced Industrial Science and Technology | BT/BI/14/042/2017 |
Ministry of Science and Technology | BT/BI/14/042/2017 |
Japan Science and Technology Agency | JPMJSP2124 |
Keywords
- Cancer therapy
- Angiogenesis
- Metastasis
- Inhibition
- Combination Wi-ACAPE
- caffeic acid phenethyl ester (CAPE)
- Propolis
- withaferin A (Wi-A)
- Ashwagandha