Broad-spectrum pharmacological activity of Australian propolis and metabolomic-driven identification of marker metabolites of propolis samples from three continents

Bhuyan, Deep Jyoti; Alsherbiny, Muhammad A.; Low, Mitchell; Zhou, Xian; Kaur, Kirandeep; Li, George; Li, Chun Guang

doi:10.1039/d1fo00127b

Cited by 24 publications

(22 citation statements)

References 111 publications

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“…We recently evaluated the AP-1 for the potential marker metabolites compared to Chinese and Brazilian propolis samples. In addition, seven common phenolics, including CAPE, artepillin C, galangin, chrysin, pinocembrin, daidzein and naringenin, were quantified in AP-1 using HPLC [49]. In the present study, almost no cell death was observed for normal macrophages (RAW 264.7) upon treatment with AP-1 and its DOX combination up to 200 µg mL −1 .…”

Section: Biochemometric and Lcms Metabolomic Identification Of Cytotoxic Metabolites Of Ap-1mentioning

confidence: 46%

“…Previously, upregulation of p-53 was reported in the MCF7 cells after treatment with Chinese [128] and Turkish propolis [129]. Our recent study showed the discriminatory metabolites of AP-1 vs. Chinese and Brazilian samples, indicating a greater antiproliferative effect of AP-1 against the MCF7 and MDA-M-B231 cells [49]. The discrepancies in the underlying cytotoxic mechanisms may be correlated to different key metabolites in the propolis samples, accounting for their differential effects on p53 expression.…”

Section: Apoptotic Proteome Profiler Array Analysis 251 Effects Of Ap-1 and Dox On Apoptotic Proteins Of The Mcf7 Cellsmentioning

confidence: 50%

“…The number of necrotic cells in the combined treatment was statistically similar to that of the vehicle control, which might indicate the ability of the synergistic combination to shift DOX-mediated necrosis to apoptosis. The observed necrotic to apoptotic shift in the synergistic combination may be attributed to the antioxidant profile of AP-1 [49]. The antioxidant-related apoptotic proteins in the MCF7 cells will be discussed in the Apoptotic Proteome Array analyses (Section 2.5).…”

Section: Flow Cytometric Analysis Of Apoptosis In the Mcf7 Cells Using Annexin V-cf Blue And 7aadmentioning

confidence: 99%

“…A growing body of evidence demonstrates the advantages of the concurrent administration of herbal medicines with chemotherapy regimens [29,[43][44][45][46][47][48] not only as cytotoxic agents but also as an antidote for chemotherapy-induced multi-organ toxicities. Propolis, for example, is a resinous substance accumulated by the bees from different types of plants with a broad spectrum of activities, including antioxidant, anti-inflammatory, antimicrobial and anticancer properties [49][50][51][52]. Australian propolis possesses superior pharmacological activity with a unique chemical fingerprint compared to its Brazilian and Chinese counterparts [49], presumably due to Australia's megadiverse and unique biodiversity.…”

Section: Introductionmentioning

confidence: 99%

“…Propolis, for example, is a resinous substance accumulated by the bees from different types of plants with a broad spectrum of activities, including antioxidant, anti-inflammatory, antimicrobial and anticancer properties [49][50][51][52]. Australian propolis possesses superior pharmacological activity with a unique chemical fingerprint compared to its Brazilian and Chinese counterparts [49], presumably due to Australia's megadiverse and unique biodiversity. Previously, prenylated stilbenes isolated from Kangaroo Island propolis [53,54] showed promising antioxidant and cytotoxic properties against 60 human tumour cell lines (NCI-60) with the IC 50 values 0.68-2.7 µM against the MCF7 cells.…”

Section: Introductionmentioning

confidence: 99%

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Metabolomic Identification of Anticancer Metabolites of Australian Propolis and Proteomic Elucidation of Its Synergistic Mechanisms with Doxorubicin in the MCF7 Cells

Alsherbiny

Bhuyan

Radwan

et al. 2021

IJMS

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The combination of natural products with standard chemotherapeutic agents offers a promising strategy to enhance the efficacy or reduce the side effects of standard chemotherapy. Doxorubicin (DOX), a standard drug for breast cancer, has several disadvantages, including severe side effects and the development of drug resistance. Recently, we reported the potential bioactive markers of Australian propolis extract (AP−1) and their broad spectrum of pharmacological activities. In the present study, we explored the synergistic interactions between AP−1 and DOX in the MCF7 breast adenocarcinoma cells using different synergy quantitation models. Biochemometric and metabolomics-driven analysis was performed to identify the potential anticancer metabolites in AP−1. The molecular mechanisms of synergy were studied by analysing the apoptotic profile via flow cytometry, apoptotic proteome array and measuring the oxidative status of the MCF7 cells treated with the most synergistic combination. Furthermore, label-free quantification proteomics analysis was performed to decipher the underlying synergistic mechanisms. Five prenylated stilbenes were identified as the key metabolites in the most active AP−1 fraction. Strong synergy was observed when AP−1 was combined with DOX in the ratio of 100:0.29 (w/w) as validated by different synergy quantitation models implemented. AP−1 significantly enhanced the inhibitory effect of DOX against MCF7 cell proliferation in a dose-dependent manner with significant inhibition of the reactive oxygen species (p < 0.0001) compared to DOX alone. AP−1 enabled the reversal of DOX-mediated necrosis to programmed cell death, which may be advantageous to decline DOX-related side effects. AP−1 also significantly enhanced the apoptotic effect of DOX after 24 h of treatment with significant upregulation of catalase, HTRA2/Omi, FADD together with DR5 and DR4 TRAIL-mediated apoptosis (p < 0.05), contributing to the antiproliferative activity of AP−1. Significant upregulation of pro-apoptotic p27, PON2 and catalase with downregulated anti-apoptotic XIAP, HSP60 and HIF-1α, and increased antioxidant proteins (catalase and PON2) may be associated with the improved apoptosis and oxidative status of the synergistic combination-treated MCF7 cells compared to the mono treatments. Shotgun proteomics identified 21 significantly dysregulated proteins in the synergistic combination-treated cells versus the mono treatments. These proteins were involved in the TP53/ATM-regulated non-homologous end-joining pathway and double-strand breaks repairs, recruiting the overexpressed BRCA1 and suppressed RIF1 encoded proteins. The overexpression of UPF2 was noticed in the synergistic combination treatment, which could assist in overcoming doxorubicin resistance-associated long non-coding RNA and metastasis of the MCF7 cells. In conclusion, we identified the significant synergy and highlighted the key molecular pathways in the interaction between AP−1 and DOX in the MCF7 cells together with the AP−1 anticancer metabolites. Further in vivo and clinical studies are warranted on this synergistic combination.

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Section: Biochemometric and Lcms Metabolomic Identification Of Cytotoxic Metabolites Of Ap-1mentioning

confidence: 46%

Section: Apoptotic Proteome Profiler Array Analysis 251 Effects Of Ap-1 and Dox On Apoptotic Proteins Of The Mcf7 Cellsmentioning

confidence: 50%

Section: Flow Cytometric Analysis Of Apoptosis In the Mcf7 Cells Using Annexin V-cf Blue And 7aadmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Metabolomic Identification of Anticancer Metabolites of Australian Propolis and Proteomic Elucidation of Its Synergistic Mechanisms with Doxorubicin in the MCF7 Cells

Alsherbiny

Bhuyan

Radwan

et al. 2021

IJMS

Self Cite

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Genome-wide screen of Escherichia coli Keio mutant line identifies genes related to propolis effect

Dibek,

Babayeva,

Elgin

et al. 2024

Eur Food Res Technol

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Propolis: chemical diversity and challenges in quality control

2022

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Propolis is a resinous natural product produced by honeybees using beeswax and plant exudates. The chemical composition of propolis is highly complex, and varies with region and season. This inherent chemical variability presents several challenges to its standardisation and quality control. The present review was aimed at highlighting marker compounds for different types of propolis, produced by the species Apis mellifera , from different geographical origins and that display different biological activities, and to discuss strategies for quality control. Over 800 compounds have been reported in the different propolises such as temperate, tropical, birch, Mediterranean, and Pacific propolis; these mainly include alcohols, acids and their esters, benzofuranes, benzopyranes, chalcones, flavonoids and their esters, glycosides (flavonoid and diterpene), glycerol and its esters, lignans, phenylpropanoids, steroids, terpenes and terpenoids. Among these, flavonoids (> 140), terpenes and terpenoids (> 160) were major components. A broad range of biological activities, such as anti-oxidant, antimicrobial, anti-inflammatory, immunomodulatory, and anticancer activities, have been ascribed to propolis constituents, as well as the potential of these compounds to be biomarkers. Several analytical techniques, including non-separation and separation methods have been described in the literature for the quality control assessment of propolis. Mass spectrometry coupled with separation methods, followed by chemometric analysis of the data, was found to be a valuable tool for the profiling and classification of propolis samples, including (bio)marker identification. Due to the rampant chemotypic variability, a multiple-marker assessment strategy considering geographical and biological activity marker(s) with chemometric analysis may be a promising approach for propolis quality assessment. Supplementary Information The online version contains supplementary material available at 10.1007/s11101-022-09816-1.

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Broad-spectrum pharmacological activity of Australian propolis and metabolomic-driven identification of marker metabolites of propolis samples from three continents

Abstract: Propolis is a by-product of honeybee farming known for its broad therapeutic benefits around the world and extensively used in the health food and beverage industry. Despite Australia being one...

Cited by 24 publications

References 111 publications

Metabolomic Identification of Anticancer Metabolites of Australian Propolis and Proteomic Elucidation of Its Synergistic Mechanisms with Doxorubicin in the MCF7 Cells

Metabolomic Identification of Anticancer Metabolites of Australian Propolis and Proteomic Elucidation of Its Synergistic Mechanisms with Doxorubicin in the MCF7 Cells

Genome-wide screen of Escherichia coli Keio mutant line identifies genes related to propolis effect

Propolis: chemical diversity and challenges in quality control

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