Pterostilbene exerts antitumor activity against human osteosarcoma cells by inhibiting the JAK2/STAT3 signaling pathway

Liu, Yanwu; Wang, Lingjuan; Wu, Yaoping; Lv, Chen; Li, Xinkui; Cao, Xiaohong; Yang, Min; Feng, Dapeng; Luo, Zhuojing

doi:10.1016/j.tox.2012.12.018

Cited by 50 publications

(41 citation statements)

References 45 publications

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“…A cell culture wound-healing assay was performed according to well-established methods (25). The cells were grown to confluence, and a linear wound was created in the confluent monolayer with a 200 mL micropipette tip.…”

Section: Analysis Of Wound Healingmentioning

confidence: 99%

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Inhibition of SIRT1 Signaling Sensitizes the Antitumor Activity of Silybin against Human Lung Adenocarcinoma Cells In Vitro and In Vivo

Liang

Yang

Wang

et al. 2014

Molecular Cancer Therapeutics

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Although silybin, a natural flavonolignan, has been shown to exhibit potent antitumor activities against various types of cancers, including lung cancer, the molecular mechanisms behind these activities remain unclear. Silent information regulator 1 (SIRT1) is a conserved NAD þ -dependent deacetylase that has been implicated in the modulation of transcriptional silencing and cell survival. Furthermore, it plays a key role in carcinogenesis through the deacetylation of important regulatory proteins, including p53. In this study, we investigated the antitumor activity of silybin towards human lung adenocarcinoma cells in vitro and in vivo and explored the role of the SIRT1 signaling pathway in this process. Silybin treatment resulted in a dose-and timedependent decrease in lung adenocarcinoma A549 cell viability. In addition, silybin exhibited strong antitumor activity illustrated by reductions in tumor cell adhesion, migratory capability, and glutathione levels and by increased apoptotic indices and reactive oxygen species levels. Silybin treatment also downregulated SIRT1 and upregulated p53 acetylation. SIRT1 siRNA (in vitro) or cambinol (a known SIRT1 inhibitor used for in vivo studies) further enhanced the antitumor activity of silybin. In summary, silybin is a potent inhibitor of lung adenocarcinoma cell growth that interferes with SIRT1 signaling, and this inhibition is a novel mechanism of silybin action that may be used for therapeutic intervention in lung adenocarcinoma treatment. Mol Cancer Ther; 13(7); 1860-72. Ó2014 AACR.

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Section: Analysis Of Wound Healingmentioning

confidence: 99%

“…Extraction of cytosolic cytochrome c was performed as described previously (25). After treatment, the cells were harvested by centrifugation at 1,000 rpm for 5 minutes.…”

Section: Extraction Of Cytosolic Cytochrome Cmentioning

confidence: 99%

Inhibition of SIRT1 Signaling Sensitizes the Antitumor Activity of Silybin against Human Lung Adenocarcinoma Cells In Vitro and In Vivo

Liang

Yang

Wang

et al. 2014

Molecular Cancer Therapeutics

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“…Recently, PTS has drawn more and more attention because of various health-promoting activities, such as antioxidant, anti-inflammatory, anti-diabetic, and prevention of age-related disease [8][9][10][11][12][13][14]. PTS possess anticancer properties against breast, colon, leukemia, liver, prostate, and lung cancers [15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

UPLC–MS method for quantification of pterostilbene and its application to comparative study of bioavailability and tissue distribution in normal and Lewis lung carcinoma bearing mice

Deng

Zhang

et al. 2015

Journal of Pharmaceutical and Biomedical Analysis

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“…Activated JAK2/STAT3 signaling pathway can modulate the expression of target genes that are involved in various physiological functions, including anti-apoptotic proteins (Bcl-xl and Bcl-2), pro-apoptotic proteins (Bax and BH3 interacting-domain death agonist) and mitochondrial apoptosis pathway-related proteins (caspase-3, caspase-9, Cyt-c and PARP) (40). Importantly, the activated JAK2/STAT3 signaling pathway has been extensively validated as a novel molecular target for the treatment of human tumors (41).…”

Section: E F C B Amentioning

confidence: 99%

A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma

et al. 2016

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Abstract. Curcumin (CUR) has been demonstrated to protect against carcinogenesis and to prevent tumor development in cancer; however, the clinical application of CUR is limited by its instability and poor metabolic properties. The present study offers an strategy for a novel CUR analogue, (1E,4E)-1,5-bis(2-bromophenyl)penta-1,4-dien-3-one (GL63), to be used as a potential therapeutic agent for hepatocellular carcinoma (HCC) in vitro and in vivo. The current study demonstrated that GL63 exhibited more potent inhibition of proliferation of HCC cells than CUR. GL63 induced G0/G1 phase cell cycle arrest and apoptosis in SK-HEP-1 cells in a dose-dependent manner, and was more potent than CUR, according to the flow cytometry data. The present study demonstrated for the first time that the inhibition of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway by GL63 resulted in a protective effect against HCC cell growth. GL63 was more effective than CUR in regulating STAT3 downstream targets, which contributed to the suppression of cell proliferation and the induction of cell apoptosis. In addition, the effects of GL63 were tested in a model of N-nitrosodiethylamine (DEN)-induced HCC in Wistar rats. Although macroscopic and microscopic features suggested that both GL63 and CUR were effective in inhibiting DEN-induced hepatocarcinogenesis, GL63 exerted a stronger effect than CUR. Immunohistochemical analysis for proliferating cell nuclear antigen demonstrated significant differences among the DEN-bearing non-treated, DEN-bearing GL63-treated and DEN-bearing, CUR-treated groups (P=0.039). It was concluded that GL63 was a potent agent able to suppress the proliferation of HCC cells by inhibition of the JAK2/STAT3 signaling pathway, with more favorable pharmacological activity than CUR, and may be a more potent compound for the prevention of DEN-induced hepatocarcinogenesis in rats than CUR.

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Pterostilbene exerts antitumor activity against human osteosarcoma cells by inhibiting the JAK2/STAT3 signaling pathway

Cited by 50 publications

References 45 publications

Inhibition of SIRT1 Signaling Sensitizes the Antitumor Activity of Silybin against Human Lung Adenocarcinoma Cells In Vitro and In Vivo

Inhibition of SIRT1 Signaling Sensitizes the Antitumor Activity of Silybin against Human Lung Adenocarcinoma Cells In Vitro and In Vivo

UPLC–MS method for quantification of pterostilbene and its application to comparative study of bioavailability and tissue distribution in normal and Lewis lung carcinoma bearing mice

A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma

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