The blueberry component pterostilbene has potent anti-myeloma activity in bortezomib-resistant cells

Chen, Gege; Xu, Zhijian; Chang, Gaomei; Hou, Jun; Hu, Liangning; Zhang, Yiwen; Yu, Dandan; Li, Bo; Chang, Shuaikang; Xie, Yongsheng; Zhang, Yong; Wei, Rong; Wu, Huiqun; Xiao, Wenqin; Sun, Xi; Yi, Tao; Dai, Bojie; Shi, Jumei; Zhu, Weiliang

doi:10.3892/or.2017.5675

Cited by 13 publications

(7 citation statements)

References 38 publications

(61 reference statements)

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“…Multiple studies have reported that natural products derived from plants are important sources of drugs that may offer significant treatment for the majority of cancer types, including colorectal and oral cancer ( 41 , 42 ). Consistent with previous studies, in which it was observed that PTE inhibited MM cell viability and induced cell cycle arrest through regulating the mitogen-activated protein kinase pathway ( 43 , 44 ), the present study demonstrated that the administration of PTE could induce MM apoptosis in vitro , and decrease tumor burden in vivo . Additionally, to the best of our knowledge, the present study was the first to report that PTE-induced MM apoptosis was metabolically dependent, via the activation of AMPK, in vitro and in vivo .…”

Section: Discussionsupporting

confidence: 92%

Pterostilbene inhibits nutrient metabolism and induces apoptosis through AMPK activation in multiple myeloma cells

Mei

et al. 2018

Int J Mol Med

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Multiple myeloma (MM) cells are characterized by an abnormal nutrient metabolism that is distinct from normal plasma cells. Pterostilbene (PTE), a bioactive component of blueberries, has been demonstrated to induce apoptosis in multiple types of cancer cell. The present study evaluated whether PTE treatment affected the survival of MM cells from a metabolic perspective, and the potential mechanisms of this. It was observed that the administration of PTE induced apoptosis, which was mediated by the increased activation of AMP-activated protein kinase (AMPK). Once activated, AMPK decreased the expression and/or activity of key lipo-genic enzymes, including fatty acid synthase and acetyl-CoA carboxylase. In addition, the activation of AMPK suppressed the downstream substrate, mechanistic target of rapamycin, which dephosphorylated eukaryotic initiation factor 4E-binding protein 1, leading to a general decrease in mRNA translation. Pre-treatment with the AMPK inhibitor compound C prior to PTE treatment compromised the anti-myeloma apoptosis effect, suggesting the critical role of AMPK in mediating PTE-induced cell toxicity. Consistent results were obtained in vivo. Finally, autophagy was adaptively upregulated subsequent to PTE treatment; the pro-apoptotic efficacy of PTE was potentiated once autophagic flux was inhibited by 3-methyladenine. Taken together, these data demonstrated that PTE exerts anti-tumor effects on MM cells via AMPK-induced nutrient suppression.

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Section: Discussionsupporting

confidence: 92%

Pterostilbene inhibits nutrient metabolism and induces apoptosis through AMPK activation in multiple myeloma cells

Mei

et al. 2018

Int J Mol Med

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“…Mitochondria benefits from the protective effects of blueberry anthocyanin extract against acrylamide toxicity [ 28 ]. Pterostilbene in blueberries can control worsened/obdurate myeloma therapy and major therapeutic myeloma of bortezomib chemotherapy [ 29 ]. Lowbush blueberry proanthocyanidins can enhance apoptosis induction in human colorectal cancer cell lines, which represents important nutritional chemoprevention of colorectal cancer [ 30 ].…”

Section: Preventive Chronic Disease Of Blueberrymentioning

confidence: 99%

Molecular Mechanism and Health Role of Functional Ingredients in Blueberry for Chronic Disease in Human Beings

Sun

Zeng

et al. 2018

IJMS

118

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Functional ingredients in blueberry have the best health benefits. To obtain a better understanding of the health role of blueberry in chronic disease, we conducted systematic preventive strategies for functional ingredients in blueberry, based on comprehensive databases, especially PubMed, ISI Web of Science, and CNKI for the period 2008–2018. Blueberry is rich in flavonoids (mainly anthocyanidins), polyphenols (procyanidin), phenolic acids, pyruvic acid, chlorogenic acid, and others, which have anticancer, anti-obesity, prevent degenerative diseases, anti-inflammation, protective properties for vision and liver, prevent heart diseases, antidiabetes, improve brain function, protective lung properties, strong bones, enhance immunity, prevent cardiovascular diseases, and improve cognitive decline. The anthocyanins and polyphenols in blueberry are major functional ingredients for preventive chronic disease. These results support findings that blueberry may be one of the best functional fruits, and further reveals the mechanisms of anthocyanins and polyphenols in the health role of blueberry for chronic disease. This paper may be used as scientific evidence for developing functional foods, nutraceuticals, and novel drugs of blueberry for preventive chronic diseases.

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“…Pterostilbene (or 3′,5′-dimethoxyresveratrol) is a compound found in blueberries and grapes [ 85 ]. Pterostilbene was investigated on H929 and bortezomib-resistant H929R cell lines, showing IC 50 values of 22.83 and 34.80 µM, respectively, after 48 h of incubation.…”

Section: Resultsmentioning

confidence: 99%

Multiple Myeloma Inhibitory Activity of Plant Natural Products

Jöhrer

Ҫiҫek

2021

Cancers

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A literature search on plant natural products with antimyeloma activity until the end of 2020 resulted in 92 compounds with effects on at least one human myeloma cell line. Compounds were divided in different compound classes and both their structure–activity-relationships as well as eventual correlations with the pathways described for Multiple Myeloma were discussed. Each of the major compound classes in this review (alkaloids, phenolics, terpenes) revealed interesting candidates, such as dioncophyllines, a group of naphtylisoquinoline alkaloids, which showed pronounced and selective induction of apoptosis when substituted in position 7 of the isoquinoline moiety. Interestingly, out of the phenolic compound class, two of the most noteworthy constituents belong to the relatively small subclass of xanthones, rendering this group a good starting point for possible further drug development. The class of terpenoids also provides noteworthy constituents, such as the highly oxygenated diterpenoid oridonin, which exhibited antiproliferative effects equal to those of bortezomib on RPMI8226 cells. Moreover, triterpenoids containing a lactone ring and/or quinone-like substructures, e.g., bruceantin, whitaferin A, withanolide F, celastrol, and pristimerin, displayed remarkable activity, with the latter two compounds acting as inhibitors of both NF-κB and proteasome chymotrypsin-like activity.

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The blueberry component pterostilbene has potent anti-myeloma activity in bortezomib-resistant cells

Cited by 13 publications

References 38 publications

Pterostilbene inhibits nutrient metabolism and induces apoptosis through AMPK activation in multiple myeloma cells

Pterostilbene inhibits nutrient metabolism and induces apoptosis through AMPK activation in multiple myeloma cells

Molecular Mechanism and Health Role of Functional Ingredients in Blueberry for Chronic Disease in Human Beings

Multiple Myeloma Inhibitory Activity of Plant Natural Products

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