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

doi:10.3390/cancers14030787

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

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

118 Downloads (Pure)

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
Article number	787
Number of pages	23
Journal	Cancers
Volume	14
Issue number	3
DOIs	https://doi.org/10.3390/cancers14030787
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
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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3390/cancers14030787Licence: CC BY

PublishedFinal published version, 4.53 MBLicence: CC BY

Cite this

Sari, A. N., Dhanjal, J. K., Elwakeel, A. A. S. A., Kumar, V., Noor Meidinna, H., Zhang , H., Ishida , Y., Terao , K., Sundar, D., C. Kaul, S., & Wadhwa, R. (2022). A Low Dose Combination of Withaferin A and Caffeic Acid Phenethyl Ester Possesses Anti-Metastatic Potential In Vitro: Molecular Targets and Mechanisms. Cancers, 14(3), Article 787. https://doi.org/10.3390/cancers14030787

@article{bac27ec17d7f41caa30ea0b2907212d5,

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

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.",

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

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

note = "Copyright: {\textcopyright} 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/).",

year = "2022",

month = feb,

day = "3",

doi = "10.3390/cancers14030787",

language = "English",

volume = "14",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "3",

}

TY - JOUR

T1 - A Low Dose Combination of Withaferin A and Caffeic Acid Phenethyl Ester Possesses Anti-Metastatic Potential In Vitro

T2 - Molecular Targets and Mechanisms

AU - Sari, Anissa Nofita

AU - Dhanjal, Jaspreet Kaur

AU - Elwakeel, Ahmed Abdelmageed Saad Ahmed

AU - Kumar, Vipul

AU - Noor Meidinna, Hazna

AU - Zhang , Huayue

AU - Ishida , Yoshiyuki

AU - Terao , Keiji

AU - Sundar, Durai

AU - C. Kaul, Sunil

AU - Wadhwa, Renu

N1 - 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/).

PY - 2022/2/3

Y1 - 2022/2/3

N2 - 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.

AB - 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.

KW - Cancer therapy

KW - Angiogenesis

KW - Metastasis

KW - Inhibition

KW - Combination Wi-ACAPE

KW - caffeic acid phenethyl ester (CAPE)

KW - Propolis

KW - withaferin A (Wi-A)

KW - Ashwagandha

UR - http://dx.doi.org/10.3390/cancers14030787

U2 - 10.3390/cancers14030787

DO - 10.3390/cancers14030787

M3 - Article

SN - 2072-6694

VL - 14

JO - Cancers

JF - Cancers

IS - 3

M1 - 787

ER -

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

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this