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

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AIST-INDIA DAILAB, National Institute of Advanced Industrial Science & Technology (AIST), Central 5-41, Tsukuba 305-8565, Japan
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School of Integrative & Global Majors (SIGMA), Tsukuba Life Science Innovation, University of Tsukuba, Tsukuba 305-8577, Japan
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Indraprastha Institute of Information Technology Delhi, Okhla Industrial Estate, Phase III, New Delhi 110-020, India
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DAILAB, Department of Biochemical Engineering & Biotechnology, Indian Institute of Technology (IIT)-Delhi, Hauz Khas, New Delhi 110-016, India
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CycloChem Co., Ltd., 7-4-5 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan
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Authors to whom correspondence should be addressed.
Academic Editor: Alastair Stewart
Cancers 2022, 14(3), 787; https://doi.org/10.3390/cancers14030787
Received: 8 December 2021 / Revised: 20 January 2022 / Accepted: 20 January 2022 / Published: 3 February 2022
Cancer therapy suffers from its high cost and high rate of adverse effects and relapse of the disease. Hence, the new (preferably natural), economic and safer therapeutic as well preventive measures have been on demand and have been subject of priority research. We have, earlier, demonstrated anticancer activity in the extracts of Ashwagandha leaves and propolis. A combination of Wi-A (an active anticancer ingredient in Ashwagandha extract) and CAPE (an active anticancer ingredient in propolis) was earlier shown to offer higher and cancer cell-selective cytotoxicity. In the present study, we report an anti-metastasis activity in the low dose combination of Wi-A and CAPE along with its mechanism of action and propose its use in cancer metastasis treatment.
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. View Full-Text
Keywords: ashwagandha; withaferin A (Wi-A); propolis; caffeic acid phenethyl ester (CAPE); combination Wi-ACAPE; inhibition; metastasis; angiogenesis; cancer therapy ashwagandha; withaferin A (Wi-A); propolis; caffeic acid phenethyl ester (CAPE); combination Wi-ACAPE; inhibition; metastasis; angiogenesis; cancer therapy
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MDPI and ACS Style

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

AMA Style

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

Chicago/Turabian Style

Sari, Anissa N., Jaspreet K. Dhanjal, Ahmed Elwakeel, Vipul Kumar, Hazna N. Meidinna, Huayue Zhang, Yoshiyuki Ishida, Keiji Terao, Durai Sundar, Sunil C. Kaul, and Renu Wadhwa. 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, no. 3: 787. https://doi.org/10.3390/cancers14030787

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