Peroxisome Proliferator-Activated Receptor-γ Contributes to the Inhibitory Effects of Embelin on Colon Carcinogenesis

Dai, Yun; Qiao, Liang; Chan, Kwok Wah; Yang, Mo; Ye, Jieyu; Ma, Juan; Zou, Bing; Gu, Qing; Wang, Jide; Pang, Roberta; Lan, Hui‐Yao; Wong, Benjamin C.Y.

doi:10.1158/0008-5472.can-08-4754

Cited by 70 publications

(51 citation statements)

References 36 publications

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“…The score of each variable was added to give a total microscopic damage score. Colonic neoplasms were diagnosed as previously described (12).…”

Section: Histopathologic Analysismentioning

confidence: 99%

“…Western blot analysis and qPCR were performed as we described (12,20), and the following primary antibodies were used: anti-glyceraldehyde-3-phosphatedehydrogenase (GAPDH, Abcam), anti-p-STAT3, anti-STAT3, antiTyr580 phoshho-SHP2 (p-SHP2), anti-SHP2 (Cell Signaling Technology), anti-IL-6Ra and anti-gp130 (Santa Cruz). All secondary antibodies were from Dako.…”

Section: Western Blot Analysis and Qpcr Assaysmentioning

confidence: 99%

“…Moreover, embelin effectively suppresses 1,2-dimethylhydrazine dihydrochloride-induced colon carcinogenesis in mice. The antitumor effects of embelin could be partly attributed to its inhibition of NF-kB activity (12). Recently, embelin was found to inhibit constitutive STAT3 activation in human cancer cell lines (13).…”

Section: Introductionmentioning

confidence: 99%

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Embelin Reduces Colitis-Associated Tumorigenesis through Limiting IL-6/STAT3 Signaling

Dai

Jiao

Teng

et al. 2014

Molecular Cancer Therapeutics

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The interleukin-6 (IL-6)/STAT3 signaling regulates survival and proliferation of intestinal epithelial cells and plays an important role in the pathogenesis of inflammatory bowel disease and colorectal cancer. Embelin is a small molecule inhibitor of X-linked inhibitor of apoptosis protein (XIAP), with antioxidant, anti-inflammatory, and antitumor activities. We previously showed that embelin inhibits the growth of colon cancer cells in vitro, and effectively suppresses 1,2-dimethylhydrazine dihydrochloride-induced colon carcinogenesis in mice. Here, we explored the antitumor effects and mechanisms of embelin on colitis-associated cancer (CAC) using the azoxymethane/dextran sulfate sodium (AOM/DSS) model, with a particular focus on whether embelin exerts its effect through the IL-6/STAT3 pathway. We found that embelin significantly reduced incidence and tumor size in CAC-bearing mice. In addition to inhibiting proliferation of tumor epithelial cells, embelin suppressed colonic IL-6 expression and secretion, and subsequently STAT3 activation in vivo. Importantly, in vitro studies have revealed that in colon cancer cells, embelin diminished both the constitutive and IL-6-induced STAT3 activation by stimulating Src homology domain 2-containing protein tyrosine phosphatase (SHP2) activity. Moreover, embelin protected mice from AOM/DSS-induced colitis before tumor development. Embelin decreased IL-1b, IL-17a, and IL-23a expression as well as the number of CD4 þ T cells and macrophages infiltrating the colonic tissues. Thus, our findings demonstrated that embelin suppresses CAC tumorigenesis, and its antitumor effect is partly mediated by limiting IL-6/STAT3 activation and Th17 immune response. Embelin may be a potential agent in the prevention and treatment of CAC. Mol Cancer Ther; 13(5); 1206-16. Ó2014 AACR.

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“…The score of each variable was added to give a total microscopic damage score. Colonic neoplasms were diagnosed as previously described (12).…”

Section: Histopathologic Analysismentioning

confidence: 99%

Section: Western Blot Analysis and Qpcr Assaysmentioning

confidence: 99%

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Embelin Reduces Colitis-Associated Tumorigenesis through Limiting IL-6/STAT3 Signaling

Dai

Jiao

Teng

et al. 2014

Molecular Cancer Therapeutics

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“…As a specific inhibitor of XIAP, embelin inhibits the action of XIAP inside cells through binding with the Smac binding site in the BIR3 domain in the XIAP protein molecule (9)(10)(11). Previous studies have demonstrated that embelin exhibits antitumor effects, and embelin at therapeutic dose can restrain the growth of various types of tumor cells including prostate cancer, pancreatic cancer, breast cancer and colon cancer (12)(13)(14)(15). According to another report, apoptosis of brain glioma cells is closely related to the mitochondrial pathway (16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Embelin-induced brain glioma cell apoptosis and cell cycle arrest via the mitochondrial pathway

Wang

Zhang

et al. 2013

Oncology Reports

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Abstract. Brain glioma is the most common malignant intracranial tumor and has become the focus of research on diseases of the central nervous system due to its high incidence and poor prognosis. As a small-molecule inhibitor of X-linked inhibitor of apoptosis protein (XIAP), embelin has the ability to specifically inhibit XIAP to control and regulate the apoptosis of various types of tumor cells. However, to date, the mechanism of action for this effect is not well understood. The aim of this study was to investigate the role that the mitochondrial pathway plays in embelin-induced brain glioma cell apoptosis and the effect of embelin on the cell cycle. Brain glioma cells were treated with different doses of embelin. The MTT method

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“…Embelin was shown to possess a broad spectrum of biological activities including antidiabetic (82), anti-inflammatory (83), and hepato-protective effects (84). In addition, embelin exhibits antitumor activity in many types of cancers such as breast (85), colon (86), prostate (87), and pancreatic cancer (88). Through computational structure-based computer screening, Wang et al (81) discovered that embelin is a potent inhibitor of X-linked inhibitor of apoptosis protein (XIAP), which partially explained its anticancer mechanism.…”

Section: Peg-derivatized Embelin As a Nanocarrier For The Delivery Ofmentioning

confidence: 99%

Polymeric Micelles: Nanocarriers for Cancer-Targeted Drug Delivery

2014

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Abstract. Polymeric micelles represent an effective delivery system for poorly water-soluble anticancer drugs. With small size (10-100 nm) and hydrophilic shell of PEG, polymeric micelles exhibit prolonged circulation time in the blood and enhanced tumor accumulation. In this review, the importance of rational design was highlighted by summarizing the recent progress on the development of micellar formulations. Emphasis is placed on the new strategies to enhance the drug/carrier interaction for improved drugloading capacity. In addition, the micelle-forming drug-polymer conjugates are also discussed which have both drug-loading function and antitumor activity.

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Peroxisome Proliferator-Activated Receptor-γ Contributes to the Inhibitory Effects of Embelin on Colon Carcinogenesis

Cited by 70 publications

References 36 publications

Embelin Reduces Colitis-Associated Tumorigenesis through Limiting IL-6/STAT3 Signaling

Embelin Reduces Colitis-Associated Tumorigenesis through Limiting IL-6/STAT3 Signaling

Embelin-induced brain glioma cell apoptosis and cell cycle arrest via the mitochondrial pathway

Polymeric Micelles: Nanocarriers for Cancer-Targeted Drug Delivery

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