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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.

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.

SUBMITTER: Sari AN

PROVIDER: S-EPMC8834371 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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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.

Sari Anissa Nofita AN Dhanjal Jaspreet Kaur JK Elwakeel Ahmed A Kumar Vipul V Meidinna Hazna Noor HN Zhang Huayue H Ishida Yoshiyuki Y Terao Keiji K Sundar Durai D Kaul Sunil C SC Wadhwa Renu R

Cancers 20220203 3

Withaferin A (Wi-A) and Caffeic Acid Phenethyl Ester (CAPE) are the bioactive ingredients of Ashwagandha (<i>Withania somnifera</i>) 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 ...[more]

PMID: 35159054

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Project description:BackgroundCaffeic acid phenethyl ester (CAPE), a natural phenolic compound, has demonstrated antibacterial effects. Dental caries etiology is multifactorial, including a cariogenic biofilm containing multispecies bacteria. However, the antibacterial property of CAPE on multispecies biofilm is unclear. The aim of this study was to assess the effect of CAPE on the formation and cariogenicity in biofilm containing Streptococcus mutans, Streptococcus oralis, and Streptococcus mitis.MethodsS. mutans (ATCC 25175), S. oralis (ATCC 35037), and S. mitis (ATCC 49456T) were employed in this investigation. Each bacterial strain was cultured in the presence of CAPE, followed by susceptibility assessment through optical density measurements at a 600 nm wavelength. Multispecies biofilm formation was achieved by co-culturing S. mutans, S. oralis, and S. mitis at a 1:1:1 ratio on hydroxyapatite-coated 96-well plates. The anti-adherence activity of CAPE on multispecies biofilm was evaluated using a crystal violet staining assay. Cariogenic gene expression level and glucosyltransferase (GTF) function in CAPE-treated mixed bacteria were evaluated using real-time PCR and enzyme activity assay, respectively. The thickness and bacterial viability in CAPE-treated multispecies biofilm were examined using confocal laser scanning microscopy.ResultsCAPE demonstrated a significant antimicrobial effect on S. mutans, S. oralis, and S. mitis (p < 0.05). The inhibition concentration 50% (IC50) of CAPE against S. mutans, S. oralis, and S. mitis ranged from 1.6-6.4 mg/ml. CAPE significantly hindered the multispecies biofilm adherence (p < 0.05). Furthermore, the expression of genes involved in acidogenicity, aciduricity, sucrose-dependent adhesion and quorum sensing mechanism and GTF activity were significantly decreased in CAPE-treated mixed bacteria (p < 0.05). In a multispecies biofilm, CAPE significantly reduced its thickness and viable bacteria population (p < 0.05). In conclusion, CAPE exhibited antimicrobial, anti-adherence and anti-cariogenic effects within a multispecies biofilm. These findings suggest the potential use of CAPE as an adjunctive anti-cariogenic agent in future dental applications.

Dataset Information

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

Publications

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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