Differential Anticancer Activity of Pterostilbene Against Three Subtypes of Human Breast Cancer Cells

Wakimoto, Rei; Ono, Misaki; Takeshima, Mikako; Higuchi, Takako; Nakano, Susumu

doi:10.21873/anticanres.12064

Cited by 20 publications

(20 citation statements)

References 29 publications

(37 reference statements)

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“…The oral administration of PT has been demonstrated to be an effective in vivo delivery method, achieving a higher plasma concentration than resveratrol 52 . Furthermore, the dietary supplementation of PT inhibited the growth of xenograft tumours of MDA-MB-468 triple-negative breast cancer cells 53 . Similarly, both low (56 mg/kg) and high doses (112 mg/kg) of PT inhibited the growth of xenograft tumours, with a human equivalent dose of approximately 4.6 and 9.1 mg/kg, respectively, according to Federal Drug Administration guidelines.…”

Section: Discussionmentioning

confidence: 97%

Inhibition of eIF2α dephosphorylation accelerates pterostilbene-induced cell death in human hepatocellular carcinoma cells in an ER stress and autophagy-dependent manner

Yang

Hung

et al. 2019

Cell Death Dis

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Hepatocellular carcinoma (HCC) is the one of the most common cancers worldwide. Because the side effects of current treatments are severe, new effective therapeutic strategies are urgently required. Pterostilbene (PT), a natural analogue of resveratrol, has diverse pharmacologic activities, including antioxidative, anti-inflammatory and antiproliferative activities. Here we demonstrated that PT inhibits HCC cell growth without the induction of apoptosis in an endoplasmic reticulum (ER) stress- and autophagy-dependent manner. Mechanistic studies indicated that the combination of salubrinal and PT modulates ER stress-related autophagy through the phospho-eukaryotic initiation factor 2α/activating transcription factor-4/LC3 pathway, leading to a further inhibition of eIF2α dephosphorylation and the potentiation of cell death. An in vivo xenograft analysis revealed that PT significantly reduced tumour growth in mice with a SK-Hep-1 tumour xenograft. Taken together, our results yield novel insights into the pivotal roles of PT in ER stress- and autophagy-dependent cell death in HCC cells.

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Section: Discussionmentioning

confidence: 97%

Inhibition of eIF2α dephosphorylation accelerates pterostilbene-induced cell death in human hepatocellular carcinoma cells in an ER stress and autophagy-dependent manner

Yang

Hung

et al. 2019

Cell Death Dis

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“…However, PTE is more metabolically stable and has exhibited more favorable pharmacological activities than resveratrol as its dimethyl ether structure enhances lipophilicity and membrane permeability ( 4 ). PTE has gained significant attention for its potent antioxidant, anti-inflammatory and anticarcinogenic properties ( 5 , 6 ). However, the mechanism of the inhibitory effect of PTE on tumor cells has not yet been completely characterized.…”

Section: Introductionmentioning

confidence: 99%

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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“…Previous studies have demonstrated that pterostilbene is an effective antioxidant with anticancer potential, which induces cell death and exhibits anti-metastatic actions ( 16 , 30 , 32 , 34 , 37 ). Furthermore, it has been demonstrated that pterostilbene triggers apoptosis in pancreatic cancer (MIA PaCa-2 and PANC-1) ( 20 , 21 ), breast cancer (MDA-MB-468, MCF-7 and MDA-MB-231) ( 18 , 19 ), lung cancer (LCC, PC9, NCI-H460, SK-MES-1 and A549) ( 22 – 24 , 29 ), osteosarcoma (SOSP-9607) ( 62 ), prostate cancer (PC-3 and LNCaP) ( 25 , 26 ), leukemia (Jurkat, Hut-78, HL60, MOLT4 and K562) ( 37 – 40 ), colon cancer (Colo 205, HCT116 and HT29) ( 27 – 29 ), bladder cancer (T24) ( 30 ), hepatocellular carcinoma (HepG2) ( 35 , 36 ), gastric carcinoma (AGS) ( 31 ) and oral cancer (SAS and OECM-1) ( 32 ) cell lines. In addition, pterostilbene exhibits autophagic effects in various types of cancer ( 29 , 30 , 38 , 39 , 42 ).…”

Section: Discussionmentioning

confidence: 99%

“…The pharmacological activities of pterostilbene mean that it may be used treat different types of diseases, including cancer, diabetes, inflammation and dyslipidemia ( 13 – 17 ). Studies have also indicated that pterostilbene may exhibit anticancer activity against various types of cancer, including breast ( 18 , 19 ), pancreatic ( 20 , 21 ), lung ( 22 – 24 ), prostate ( 25 , 26 ), colorectal ( 27 – 29 ), bladder ( 30 ), gastric ( 31 ) and oral cancer ( 32 – 34 ), as well as hepatocellular carcinoma ( 35 , 36 ) and leukemia ( 37 – 40 ). The results of in vitro and in vivo studies have demonstrated that pterostilbene induces apoptotic and/or autophagic cell death ( 29 , 32 , 41 , 42 ).…”

Section: Introductionmentioning

confidence: 99%

Pterostilbene modulates the suppression of multidrug resistance proteinï¿½1 and triggers autophagic and apoptotic mechanisms in cisplatin-resistant human oral cancer CAR cells via AKT signaling

Chang

Chiang³

et al. 2018

Int J Oncol

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Pterostilbene is a natural polyphenolic compound that is primarily found in fruits, such as blueberries and has a similar structure to resveratrol. Pterostilbene exhibits antioxidant, anti-inflammatory and antitumor activity but the effects of pterostilbene on drug-resistant oral cancer cells and its underlying mechanisms of action have not yet been explored. Therefore, the present study was performed to clarify the anticancer effects of pterostilbene on cisplatin-resistant human oral cancer CAR cells. The results demonstrated that CAR cells exhibited marked shrinkage, cell membrane breakage and autophagic vacuole formation following treatment with pterostilbene. Pterostilbene also effectively inhibited cell viability and suppressed cell confluence in a time- and concentration-dependent manner. Probing with acridine orange, monodansylcadaverine and LysoTracker Red demonstrated that the number of acidic vesicular organelles was increased, indicating increased autophagy. Furthermore, Heochst 33342 staining determined that DNA condensation, a characteristic of apoptosis, was enhanced following treatment with pterostilbene. Furthermore, pterostilbene upregulated mRNA levels of LC3-II and Atg12, as well as the expression of Atgs/Beclin-1/LC3-associated signaling, suggesting that it enhances autophagy. The autophagy inhibitors 3-methyladenine and chloroquine were used to confirm that pterostilbene induces autophagy. It was also determined that pterostilbene triggered caspase-dependent apoptosis by directly testing DNA breakage and using the pan-caspase inhibitor carbobenzoxyvalyl-alanyl-aspartyl fluoromethyl ketone. The results demonstrated that pterostilbene mediates the apoptosis of CAR cells via the intrinsic apoptotic cascade. In addition, pterostilbene inhibited MDR1 expression and the phosphorylation of AKT on the Ser473 site in CAR cells. Therefore, pterostilbene may elicit an oral anticancer response in drug-resistant cells and may be used as a chemotherapeutic adjuvant to treat patients with oral cancer.

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Differential Anticancer Activity of Pterostilbene Against Three Subtypes of Human Breast Cancer Cells

Cited by 20 publications

References 29 publications

Inhibition of eIF2α dephosphorylation accelerates pterostilbene-induced cell death in human hepatocellular carcinoma cells in an ER stress and autophagy-dependent manner

Inhibition of eIF2α dephosphorylation accelerates pterostilbene-induced cell death in human hepatocellular carcinoma cells in an ER stress and autophagy-dependent manner

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

Pterostilbene modulates the suppression of multidrug resistance proteinï¿½1 and triggers autophagic and apoptotic mechanisms in cisplatin-resistant human oral cancer CAR cells via AKT signaling

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