Platyphylloside Isolated from Betula platyphylla is Antiproliferative and Induces Apoptosis in Colon Cancer and Leukemic Cells

Lee, Jooeun; Thủy, Nguyễn Thị Thanh; Lee, Jina; Cho, Namki; Yoo, Hee Min

doi:10.3390/molecules24162960

Cited by 16 publications

(12 citation statements)

References 29 publications

(42 reference statements)

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“…Values shown are the means ± Standard Error of Mean (SEM). The data were analyzed using one-way Student's t-test, and p values less than 0.05 (*p < 0.05, **p < 0.01, ***p < 0.001) were considered statistically significant (Lee et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

(+)-Dehydrovomifoliol Alleviates Oleic Acid-Induced Lipid Accumulation in HepG2 Cells via the PPARα–FGF21 Pathway

Zheng

Wei

et al. 2021

Front. Pharmacol.

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An overload of hepatic fatty acids, such as oleic acid is a key trigger of non-alcoholic fatty liver disease (NAFLD). Here, we investigated whether Artemisia frigida, a valuable traditional medicine used to treat various diseases, could mitigate OA-induced lipid accumulation in HepG2 cells. Then, to identify the active substances in A. frigida, a phytochemistry investigation was conducted using a bioassay-guided isolation method. Consequently, one terpene (1) and one flavone (2) were identified. Compound 1 ((+)-dehydrovomifoliol) exhibited potent effects against lipid accumulation in OA-induced HepG2 cells, without causing cyto-toxicity. Notably, treatment with (+)-dehydrovomifoliol decreased the expression levels of three genes related to lipogenesis (SREBP1, ACC, and FASN) and increased those of three genes related to fatty acid oxidation (PPARα, ACOX1, and FGF21). In addition, similar results were observed for SREBP1, PPARα, and FGF21 protein levels. The effects of (+)-dehydrovomifoliol were partially reversed by treatment with the PPARα antagonist GW6471, indicating the important role of the PPARα–FGF21 axis in the effects of (+)-dehydrovomifoliol. Based on its effects on hepatic lipogenesis and fatty acid oxidation signaling via the PPARα–FGF21 axis, (+)-dehydrovomifoliol isolated from A. frigida could be a useful early lead compound for developing new drugs for NAFLD prevention.

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Section: Discussionmentioning

confidence: 99%

(+)-Dehydrovomifoliol Alleviates Oleic Acid-Induced Lipid Accumulation in HepG2 Cells via the PPARα–FGF21 Pathway

Zheng

Wei

et al. 2021

Front. Pharmacol.

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“…Human Jurkat cell lines were obtained from the American Type Culture Collection (ATCC) and were cultured according to standard mammalian tissue culture protocols. Cell viability was evaluated using the MTS assay 48 h after treatment with lesbicoumestan, as described in our previous publication [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

“…The cell percentages were acquired using FlowJo software (Version 10, BD Biosciences). The detailed method followed the manufacturer’s instructions, as described in our previous publication [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

Anticancer Activity of Lesbicoumestan in Jurkat Cells via Inhibition of Oxidative Stress-Mediated Apoptosis and MALT1 Protease

et al. 2021

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This study explores the potential anticancer effects of lesbicoumestan from Lespedeza bicolor against human leukemia cancer cells. Flow cytometry and fluorescence microscopy were used to investigate antiproliferative effects. The degradation of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) was evaluated using immunoprecipitation, Western blotting, and confocal microscopy. Apoptosis was investigated using three-dimensional (3D) Jurkat cell resistance models. Lesbicoumestan induced potent mitochondrial depolarization on the Jurkat cells via upregulated expression levels of mitochondrial reactive oxygen species. Furthermore, the underlying apoptotic mechanisms of lesbicoumestan through the MALT1/NF-κB pathway were comprehensively elucidated. The analysis showed that lesbicoumestan significantly induced MALT1 degradation, which led to the inhibition of the NF-κB pathway. In addition, molecular docking results illustrate how lesbicoumestan could effectively bind with MALT1 protease at the latter’s active pocket. Similar to traditional 2D cultures, apoptosis was markedly induced upon lesbicoumestan treatment in 3D Jurkat cell resistance models. Our data support the hypothesis that lesbicoumestan is a novel inhibitor of MALT1, as it exhibited potent antiapoptotic effects in Jurkat cells.

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“…To assess antiproliferative effects in the presence of compounds isolated from the roots of L. bicolor , cell viability was measured using an MTS assay, as described previously …”

Section: Methodsmentioning

confidence: 99%

Antiproliferative Pterocarpans and Coumestans from Lespedeza bicolor

et al. 2019

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Chromatographic purification of a methanol extract of the roots of Lespedeza bicolor led to the isolation of four new pterocarpans (1− 4), two new coumestans (6 and 7), two new arylbenzofurans (8 and 9), and the known pterocarpan 1-methoxyerythrabyssin II (5). Their structures were identified using NMR spectroscopy, UV spectroscopy, and mass spectrometry. Cytotoxicity assays showed that compounds 1−9 exerted antiproliferative effects on blood cancer cells. Of these compounds, 1 and 6 induced mitochondrial depolarization and induced apoptosis in Jurkat cells. These compounds promoted cell death by inducing cell-cycle arrest at the G1 stage, reducing levels of BCL2, and increasing cleavage of PARP-1. These findings indicate that 1 and 6 are possible lead compounds for the treatment of human leukemia cells via intracellular signaling.Lespedeza bicolor Turcz. plants, of the family Leguminosae, are distributed widely across Eastern North America and Eastern Asia. 1 Plants in the genus Lespedeza have been used traditionally in the treatment of diuresis, skin diseases, cough, and fever. 2,3 Moreover, components from the roots of L. bicolor were reported to inhibit bacterial neuraminidase and cancer cell growth. 4,5 Compounds isolated from L. bicolor include alkaloids, flavonoids, sterols, and terpenenoids, which have been investigated for anti-inflammatory, antioxidative, cytotoxic, and blood glucose-reducing effects. 4−8 Flavonoids predominate in the genus Lespedeza, and several common compounds of this type have been isolated from L. bicolor. 9 Recently, two prenylated isoflavanones and six pterocarpans were purified from the stem bark of L. bicolor, 10 with the six pterocarpans showing inhibitory activity against bacterial neuraminidase. 5 In addition, four other pterocarpans exhibited an antiproliferative effect against cancer cell lines. 11 The present report describes the isolation from the roots of L. bicolor of four new pterocarpans (1−4), two new coumestans (6 and 7), two new arylbenzofurans (8 and 9), and the known pterocarpan 1-methoxyerythrabyssin II (5). 12 Nine isolated compounds (1−9) were analyzed for their potential antileukemic activities in Jurkat leukemia cells. 13 The present study revealed that pterocarpans and coumestans isolated from L. bicolor exerted potent cytotoxic effects, including the induction of apoptosis in Jurkat cells. The induction of apoptosis was investigated by the evaluation of the protein expression of Bcl-2 and cleaved PARP using Western blotting. To elucidate the antioxidant effects of the compounds, the reduction of mitochondrial tetramethylrhod-amine methyl ester (TMRM) and the induction of cell-cycle arrest were evaluated.

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Platyphylloside Isolated from Betula platyphylla is Antiproliferative and Induces Apoptosis in Colon Cancer and Leukemic Cells

Cited by 16 publications

References 29 publications

(+)-Dehydrovomifoliol Alleviates Oleic Acid-Induced Lipid Accumulation in HepG2 Cells via the PPARα–FGF21 Pathway

(+)-Dehydrovomifoliol Alleviates Oleic Acid-Induced Lipid Accumulation in HepG2 Cells via the PPARα–FGF21 Pathway

Anticancer Activity of Lesbicoumestan in Jurkat Cells via Inhibition of Oxidative Stress-Mediated Apoptosis and MALT1 Protease

Antiproliferative Pterocarpans and Coumestans from Lespedeza bicolor

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