Phloretin-induced apoptosis in B16 melanoma 4A5 cells by inhibition of glucose transmembrane transport

doi:10.1016/S0304-3835(97)00271-1

Cancer Letters

Volume 119, Issue 2, 11 November 1997, Pages 207-212

https://doi.org/10.1016/S0304-3835(97)00271-1 Get rights and content

Abstract

Phloretin, a naturally occurring dihydrochalcone, is known to inhibit tumor cell growth in vitro and in vivo. To clarify the anti-tumor effects of phloretin, its apoptosis-inducing effects in B16 melanoma 4A5 cells were examined. Phloretin induced the internucleosomal DNA fragmentation typical of apoptosis in B16 melanoma cells. The addition of extracellular glucose remarkably inhibited the phloretin-induced apoptosis in the cells. When apoptosis was strongly induced in the B16 cells by phloretin, protein kinase C activity was inhibited in the cells. Our results suggest that phloretin induced apoptosis in B16 melanoma 4A5 cells mainly through the inhibition of glucose transmembrane transport. Inhibition of protein kinase C activity by phloretin probably promotes the ratio of apoptotic cells in the cells.

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Silene vulgaris (Moench) Garcke subsp. macrocarpa is a wild herbaceous plant known for its nutraceutical properties, and use in folk medicine. This study investigates the anti-cancer properties of S. vulgaris extracts.
The leaves and roots of S. vulgaris were extracted by the Soxhlet extractor with ethanol, their phenolic content was determined by RTHPLC-DAD. By using squamous cell carcinoma cells and bone marrow-derived macrophages, we defined the ability of S. vulgaris extracts to kill tumour cells and suppress the tumour-promoting phenotype of macrophages.
A total of 21 phenolic compounds were detected, among which dihydrochalcones phloredzin and phloretin were most abundant, encompassing about 70% of the whole polyphenolic content in leaf extract. In the root extract, 45.75% of the polyphenolic compounds are flavonoids (epicatechin, epicatechin gallate, and avicularin). The leaf and the root extracts exhibit cytotoxic activity against A431 tumour cells. The highest cytotoxic activity was observed by root extract (IC50 =102.65 vs 173.26 µg /mL). Interestingly, this extract also most potently induces the anti-tumour properties of BMDMs by decreasing the expression of genes typically expressed by tumour-associated macrophages, such as ARG1, CD163, CD209, TREM2, FIZZ1, MMP9, and CCL17, and suppressing the expression of the angiogenic factors EGF and VEGF. In contrast, the leaf extract promotes the expression of pro-inflammatory mediators IL-6, TNF-α, and iNOS in macrophages.
The results highlight the anti-tumour properties of S. vulgaris leaves and roots, which underscore its effectiveness in traditional medicine and may open new avenues for its use in therapeutic anti-cancer applications.
Palladium-Catalyzed Multicomponent Cascade Reaction of 3-Hydroxypropionitrile: Synthesis of Substituted Dihydrochalcones
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Direct access to substituted dihydrochalcones from the easily available starting materials 3-hydroxypropionitrile derivatives and arylboronic acids is described. The procedure involves a multicomponent aryl addition/hydroxyl elimination/reduction Heck approach in the presence of a Pd catalyst with excellent functional group tolerance and a wide range of substrates. In addition, mixed 1,3-diarylation of 3-hydroxypropanenitrile using two arylboronic acids with different electronic properties was also achieved.
Innovative hydrogel containing polymeric nanocapsules loaded with phloretin: Enhanced skin penetration and adhesion
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Citation Excerpt :
In contrast, at concentrations of 20 or 50 μM, less than 2% inhibition of cell growth occurred. In another study, 150 μM phloretin induced apoptosis in approximately 95% of B16 mouse melanoma 4A5 after 24 h [54]. The results presented here are based on cell treatment using 10 μM phloretin, which suggests the superiority of the nanocapsules.
Dermatological applications of phloretin are restricted by its poor aqueous solubility. Nanotechnology has been proposed as strategy to increase the apparent drug solubility in aqueous media. This study aimed to develop, characterize, and evaluate the antitumoral effects and safety of polymeric nanocapsules containing phloretin (NCPhl). Further, to incorporate NC-Phl in an innovative semi-solid formulation (HG-NCPhl) to evaluate its performance using porcine skin model. NC-Phl was prepared and the effects in MRC5, HACAT, and SK-mel28 cells were evaluated. Hydrogels were prepared with Lecigel ® and characterized for their nanotechnological properties, adhesion (in vitro washability), and penetration/permeation studies in porcine skin. NC-Phl had a cytotoxic effect against Sk-Mel-28 cells and the population doubling time was increased upon treatment with NC-Phl for longer culture periods; notably when cells were treated for 72 h and then followed for 7 days after the treatment was removed (p < 0.05). HG-NC-Phl was considered adhesive and had a higher capacity to penetrate all skin layers compared with HG-Phl (p < 0.05). The innovative hydrogel HGNC-Phl promoted a drug-reservoir in the stratum corneum and higher penetration of the flavonoid into the epidermis. Therefore, this approach can be considered as a platform to establish versatile dermatological solutions for both cosmeceutics and melanoma therapy.
Dermatological applications of the flavonoid phloretin
2020, European Journal of Pharmacology
Citation Excerpt :
The inhibition of glucose trans-membrane transport by phloretin at different concentrations was also shown in erythrocytes of diabetic patients (Hu et al., 2000) as well as human liver cancer cells (Wu et al., 2009) and breast cancer cells (Wu et al., 2018). In addition, phloretin (0.15 mM) inhibited about 75% of protein kinase C activity in B16 melanoma 4A5 cells (Kobori et al., 1997). This is important because downregulation of protein kinase C activity induces apoptosis.
Botanical molecules are known to have the ability to counteract ultraviolet radiation-induced skin damage. The interest in the development of natural compound-based products for the prevention of solar ultraviolet radiation-induced skin photoaging, melasma, and photocarcinogenesis has been increasing. Recently, the flavonoid phloretin has attracted the attention of researchers in the dermatological field for application in cosmetics and therapeutics. In addition to its antioxidant activity, phloretin has been shown to have properties such as anti-aging and depigmenting effects. In this study, we review the dermatological treatments with phloretin for conditions such as melasma, photoaging, acne, and melanoma. Phloretin has been shown to inhibit elastase and matrix metalloproteinase-1 activity, to reduce cellular tyrosinase activity and melanin content, and induce apoptosis in B16 mouse melanoma 4A5 cells. An in vivo study showed that phloretin, applied topically to the dorsal skin of mice, suppressed the 12-O-tetradecanoylphorbol 13-acetate-induced expression of COX-2, a critical molecular target of many chemopreventive, as well as anti-inflammatory agents. Phloretin can penetrate the skin; nevertheless, its penetration profile in different skin layers has not yet been evaluated. Despite its health benefits, phloretin application has been limited because of its photoinstability and poor aqueous solubility, among other limitations. Therefore, we reviewed the recent advances in pharmaceutical applications such as the use of nanotechnology, in order to improve the cutaneous availability of phloretin. In this review, we also focus on the oral application, product development challenges, and recent progress and future research directions on phloretin.
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Selective hydrogenation of α, β-unsaturated ketones is an important catalytic process in organic synthesis and industrial production [1–4]. And the selective hydrogenation of the CC bond functional group is a significant method for the production of saturated ketones, which are key intermediates for synthesizing biologically active compounds such as HIV-I protease inhibitors [5,6]. In recent years, although non-noble transition metal like copper was investigated as an economical catalyst alternative [7], much more studies have still used different noble transition metal catalysts for this kind reaction, such as Ru [8,9], Pt [10,11], Ir [12,13], Pt/Re [14], Au [15,16], and Pd [4,17–20].
A thermoregulated phase-transfer Pd nanocatalyst was explored firstly and shown to be highly efficient and recyclable in the atmospheric hydrogenation of α, β-unsaturated ketones. Under optimized reaction conditions, the conversion of chalcone and the selectivity of dihydrochalcone were 99% and 98%, respectively. The catalyst can be easily separated from the product and used directly for four times without evident loss in activity and selectivity. The turnover frequency (TOF) for the atmospheric hydrogenation of chalcone was 870 h⁻¹, which to the best of our knowledge was the highest value ever reported among transition metal nanocatalysts.

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¹: Current address: National Research Institute of Fisheries Sciences, Ministry of Agriculture, Forestry and Fisheries, 2-12-4 Fukuura, Yokohama, Kanagawa 236, Japan.

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Phloretin-induced apoptosis in B16 melanoma 4A5 cells by inhibition of glucose transmembrane transport

Abstract

Biochem. Biophys. Res. Commun.

J. Steroid Biochem. Mol. Biol.

Cancer Lett.

Exp. Cell Res.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Exp. Cell Res.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

Quercetin inhibits hexose transport in a human diploid fibroblast

J. Membr. Biol.