Mechanisms involved in the cytotoxic action of Brazilian propolis and caffeic acid against HEp-2 cells and modulation of P-glycoprotein activity

Silva, Lívia M da; Frión-Herrera, Yahima; Bartolomeu, Ariane Rocha; Gorgulho, Carolina Mendonça; Sforcin, José Maurício

doi:10.1111/jphp.12789

Cited by 16 publications

(8 citation statements)

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“…1c), the B. dracunculifolia extract reduced the transcriptional levels of the analyzed genes. Some authors have reported that the extract can modulate the expression levels of proapoptotic genes, such as caspase 3, as observed in this study [43, 44], confirming the beneficial and hepatoprotective effects of the extract, which presents antioxidant and anti-inflammatory molecules [26, 27, 45]. In our study, high expression levels of the antiapoptotic gene bcl-2 were observed in cells treated with P. barbatus , which can facilitate the progression of hepatic fibrosis [46].…”

Section: Discussionsupporting

confidence: 64%

Cellular and molecular effects of Baccharis dracunculifolia D.C. and Plectranthus barbatus Andrews medicinal plant extracts on retinoid metabolism in the human hepatic stellate cell LX-2

Silva

Caetano

Pereira

et al. 2019

BMC Complement Altern Med

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Background Chronic hepatic diseases are serious problems worldwide, which may lead to the development of fibrosis and eventually cirrhosis. Despite the significant number of people affected by hepatic fibrosis, no effective treatment is available. In the liver, hepatic stellate cells are the major fibrogenic cell type that play a relevant function in chronic liver diseases. Thus, the characterization of components that control the fibrogenesis in the hepatic stellate cells is relevant in supporting the development of innovative therapies to treat and/or control liver fibrosis. The present study investigated the effects of Baccharis dracunculifolia D.C. and Plectranthus barbatus Andrews medicinal plant extracts in LX-2 transdifferentiation. Methods LX-2 is a human immortalized hepatic stellate cell that can transdifferentiate in vitro from a quiescent-like phenotype to a more proliferative and activated behavior, and it provides a useful platform to assess antifibrotic drugs. Then, the antifibrotic effects of hydroalcoholic extracts of Baccharis dracunculifolia and Plectranthus barbatus medicinal plants on LX-2 were evaluated. Results The results in our cellular analyses, under the investigated concentrations of the plant extracts, indicate no deleterious effects on LX-2 metabolism, such as toxicity, genotoxicity, or apoptosis. Moreover, the extracts induced changes in actin filament distribution of activated LX-2, despite not affecting the cellular markers of transdifferentiation. Consistent effects in cellular retinoid metabolism were observed, supporting the presumed activity of the plant extracts in hepatic lipids metabolism, which corroborated the traditional knowledge about their uses for liver dysfunction. Conclusion The combined results suggested a potential hepatoprotective effect of the investigated plant extracts reinforcing their safe use as coadjuvants in treating imbalanced liver lipid metabolism.

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Section: Discussionsupporting

confidence: 64%

Cellular and molecular effects of Baccharis dracunculifolia D.C. and Plectranthus barbatus Andrews medicinal plant extracts on retinoid metabolism in the human hepatic stellate cell LX-2

Silva

Caetano

Pereira

et al. 2019

BMC Complement Altern Med

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“…Here, EEP affected the viability of MCF-7 cells using concentrations higher than 50 μg/ml after 72 hr. These cells were more resistant to EEP action than canine osteosarcoma and laryngeal epidermoid carcinoma HEp-2 cells (Cinegaglia, Bersano, Búfalo, & Sforcin, 2013;Silva et al, 2017). Lower concentrations (<20 μg/ml) of Brazilian green propolis did not affect MCF-7 cells (Kamiya, Nishihara, Hara, & Adachi, 2012).…”

Section: Discussionmentioning

confidence: 82%

“…Brazilian green propolis exerted a cytotoxic activity against lung cancer A549 cells and laryngeal epidermoid carcinoma HEp-2 cells by inducing apoptosis (Fri on-Herrera, Díaz-García, Ruiz-Fuentes, Rodríguez-Sánchez, & Sforcin, 2015;Silva, Fri on-Herrera, Bartolomeu, Gorgulho, & Sforcin, 2017). This ethanol solution extract of propolis (EEP) also enhanced the action of an antitumor agent (carboplatin) against canine osteosarcoma in vitro (Bernardino, Bersano, Lima Neto, & Sforcin, 2018).…”

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confidence: 99%

Brazilian green propolis: A novel tool to improve the cytotoxic and immunomodulatory action of docetaxel on MCF‐7 breast cancer cells and on women monocyte

Cardoso

Santiago

Conti

et al. 2021

Phytotherapy Research

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Docetaxel (DTX) is used against breast cancer despite its side effects such as toxicity and immunosuppression. Here we investigated the cytotoxic and immunomodulatory effects of the ethanol solution extract of propolis (EEP) in combination with DTX on MCF‐7 breast cancer cells and on women's monocyte. The cytotoxic potential of EEP + DTX was assessed by MTT assay and the type of tumor cell death was evaluated by flow cytometry. The effects of EEP + DTX on the migration and invasion of MCF‐7 cells were analyzed. Cytokine production by monocytes was assessed by ELISA and the expression of cell surface markers was evaluated by flow cytometry. We also assessed the fungicidal activity of monocytes against Candida albicans and the generation of reactive oxygen species (ROS). Finally, the impact of the supernatants of treated monocytes in the viability, migration, and invasiveness of tumor cells was assessed. EEP enhanced the cytotoxicity of DTX alone against MCF‐7 cells by inducing necrosis and inhibiting their migratory ability. EEP + DTX exerted no cytotoxic effects on monocytes and stimulated HLA‐DR expression, TNF‐α, and IL‐6 production, exerted an immunorestorative action in the fungicidal activity, and reduced the oxidative stress. Our findings have practical implications and reveal new insights for complementary medicine.

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“…Thus, the potential of F1 fraction on apoptosis induction of MDA-MB-231 cells was evaluated, and the results showed that treatment of MDA-MB-231 cells with the F1 fraction significantly induced apoptosis. Propolis also induces apoptosis and inhibits cell growth by causing cell cycle S or G2/M phase arrest in different cancer cell types [24][25][26].…”

Section: Discussionmentioning

confidence: 99%

Apoptotic Potential and Chemical Composition of Jordanian Propolis Extract against Different Cancer Cell Lines

Abutaha

2020

J. Microbiol. Biotechnol.

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Propolis is a resinous substance that is collected by Apis mellifera from plant sources and is used in traditional medicine. To study the phytochemical constituents and apoptotic potential of Jordanian propolis extract against different cancer cell lines, propolis was extracted using methanol, hexane, and ethyl acetate and was fractionated using chromatographic methods. Cytotoxicity was assessed using MTT and LDH assays. The apoptotic potential was investigated using florescence microscopy, multicaspase assay, Annexin-V and dead cell assay, and cell cycle assay. The phytochemical constituents were analyzed using GC-MS. The methanol extract of propolis exhibited cytotoxic potential against all cell lines tested. The IC 50 values of the methanol extract were 47.4, 77.8, 91.2, and 145.0 μg/ml for HepG2, LoVo, MDAMB231, and MCF7 cell lines, respectively. The IC 50 values of the F1 fraction were 31.6 (MDAMB231), 38.9 (HepG2), 36.7 (LoVo) and 75.5 (MCF7) μg/ml. On further purification using thin-layer chromatography, the IC 50 values of the F1-3 fraction were found to be 84.31(HepG2), 79.2 (MCF7), 70.4 (LoVo), and 68.9 (MDAMB231) μg/ml, respectively. The anticancer potential of the F1 fraction was confirmed through the induction of apoptosis and cell cycle arrest at the G0/G1 phase. The GC-MS analysis of the F1 fraction revealed the presence of 3-methyl-4isopropylphenol (29.44%) as a major constituent. These findings indicate the potential of propolis extract as a cancer therapy. However, further investigation is required to assess the acute and subacute toxicity of the most active fraction.

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Mechanisms involved in the cytotoxic action of Brazilian propolis and caffeic acid against HEp-2 cells and modulation of P-glycoprotein activity

Abstract: Propolis exerted cytotoxic effects on HEp-2 cells, and the mechanisms are discussed, showing its potential as an antitumour drug.

Cited by 16 publications

References 30 publications

Cellular and molecular effects of Baccharis dracunculifolia D.C. and Plectranthus barbatus Andrews medicinal plant extracts on retinoid metabolism in the human hepatic stellate cell LX-2

Cellular and molecular effects of Baccharis dracunculifolia D.C. and Plectranthus barbatus Andrews medicinal plant extracts on retinoid metabolism in the human hepatic stellate cell LX-2

Brazilian green propolis: A novel tool to improve the cytotoxic and immunomodulatory action of docetaxel on MCF‐7 breast cancer cells and on women monocyte

Apoptotic Potential and Chemical Composition of Jordanian Propolis Extract against Different Cancer Cell Lines

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