A Low Dose Combination of Withaferin A and Caffeic Acid Phenethyl Ester Possesses Anti-Metastatic Potential In Vitro: Molecular Targets and Mechanisms

Anissa Nofita Sari, Jaspreet Kaur Dhanjal, Ahmed Abdelmageed Saad Ahmed Elwakeel, Vipul Kumar, Hazna Noor Meidinna, Huayue Zhang , Yoshiyuki Ishida , Keiji Terao , Durai Sundar, Sunil C. Kaul, Renu Wadhwa

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2 Citations (Scopus)
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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 languageEnglish
Article number787
Number of pages23
JournalCancers
Volume14
Issue number3
DOIs
Publication statusPublished - 3 Feb 2022
Externally publishedYes

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/).

Keywords

  • Cancer therapy
  • Angiogenesis
  • Metastasis
  • Inhibition
  • Combination Wi-ACAPE
  • caffeic acid phenethyl ester (CAPE)
  • Propolis
  • withaferin A (Wi-A)
  • Ashwagandha

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