Inhibitory effect of cucurbitacin E on pancreatic cancer cells growth via STAT3 signaling

Sun, Chunyan; Zhang, Meixia; Shan, Xiaolei; Zhou, Xingtong; Jiao, Yang; Wang, Yanli; Li‐Ling, Jesse; Deng, Yihui

doi:10.1007/s00432-009-0698-x

Cited by 62 publications

(41 citation statements)

References 31 publications

(32 reference statements)

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“…Regarding pancreatic cancer, the work of Sun et al (2010) showed that cucurbitacin E of the family of triterpenoids isolated from plants can reduce the phosphorylation of STAT3, leading to inhibition of cell growth, increased expression of p53 and induction of apoptosis of cancer cells. Indeed, p53 can arrest cell cycle progression at different points and induce apoptosis of cells whose growth has become uncontrolled.…”

Section: Pancreatic Cancermentioning

confidence: 99%

Dietary compounds as potent inhibitors of the signal transducers and activators of transcription (STAT) 3 regulatory network

et al. 2012

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Signal transducers and activators of transcription (STAT) proteins were described as a family of latent cytosolic transcription factors whose activation is dependent on phosphorylation via growth factor-and cytokine-membrane receptors including interferon and interleukin, or by nonreceptor intracellular tyrosine kinases, including Src. A vast majority of natural substances are capable of modulating mitogenic signals, cell survival, apoptosis, cell cycle regulation, angiogenesis as well as processes involved in metastasis development. The inhibition of STAT3 phosphorylation by natural and dietary compounds leads to decreased protein expression of STAT3 targets essentially involved in regulation of the cell cycle and apoptotic cell death. This review details the cell signaling pathways involving STAT transcription factors as well as the corresponding compounds from nature able to interfere with this regulatory system in human cancer.The family of STAT transcription factors Structure and function STAT (signal transducers and activators of transcription) proteins were originally described as a family of cytoplasmic transcription factors. In mammals, seven members of this family, each consisting of 750-900 amino acids, have been identified: STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6. These transcription factors act as dimers (homo-or hetero-dimers), and their activation is dependent on their phosphorylation or via membrane receptors stimulated by either extracellular factors, including interferon (IFN) and interleukin (IL-6), or by intracellular kinases independent of receptors, including Src. Activation of STATs is usually transient and highly regulated. STAT proteins contain seven conserved structural and functional domains ( First, the amino terminal NH 2 domain is involved in the dimerization of STAT proteins and in the stabilization of the interaction established between these dimers and DNA response elements (Braunstein et al. 2003;Mertens et al. 2006). The coiled-coil domain is responsible for controlling the process of import and export of proteins into and from the nucleus (Schindler et al. 2007). The domain that binds DNA, or the DBD (DNA binding domain), is involved in the physical interaction with STAT3-response elements in the promoters of target genes. With the exception of STAT2, all activated STAT homodimers bind directly to a palindromic sequence, the GAS (IFN-gammaactivated site), TTTCCNGGAAA (Becker et al. 1998). The ''linker'' domain localizes the active dimer to the DNA binding site. The transcriptional activation domain (TAD) contains sites of phosphorylation of serine residues that allow the recruitment of coactivators such as RNA polymerase II, histone acetyltransferase (HAT) (Paulson et al. 2002), histone deacetylase (HDAC) (Rascle et al. 2003) and chromatin modification complexes.Finally, two sites are particularly critical for the activity of STAT. These are the SH2 domain (Src homology 2, amino acids 575-680), which is linked to the DBD by the linker domain, and a conser...

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Section: Pancreatic Cancermentioning

confidence: 99%

Dietary compounds as potent inhibitors of the signal transducers and activators of transcription (STAT) 3 regulatory network

et al. 2012

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“…However, the same research group described that the effects of cucurbitacin B on K562 leukemia cells were related to the inhibition of STAT-3 expression (Chan et al, 2010b). Another recent work on the effects of cucurbitacin E on pancreatic cells demonstrated an association with inhibition of STAT 3 (Sun et al, 2010). The STAT proteins have dual roles as cytoplasmic signaling proteins and nuclear transcription factors.…”

Section: Discussionmentioning

confidence: 99%

“…Some reports attributed in vitro and in vivo anticancer activities to the cucurbitacins (Fang et al, 1984;Duncan et al, 1996;Chan et al, 2010a;Sun et al, 2010). Jayaprakasam and co-workers demonstrated the cytotoxic properties of cucurbitacins B, D, E and I, isolated from the fruits of Cucurbita andreana, against colon, breast, lung and central nervous system cancer cell lines (Jayaprakasam et al, 2003).…”

Section: Research Articlementioning

confidence: 99%

In vitroandin vivoanticancer properties of cucurbitacin isolated fromCayaponia racemosa

Militão

Dantas

Ferreira

et al. 2012

Pharmaceutical Biology

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“…Recently, several triterpenoids from various plants have been reported to feature antiproliferative [51][52][53] and anti-invasive [54,55] bioactive components. More than 50 triterpenoids have been isolated from bitter melon, but their biological activities have yet to be explored in detail.…”

Section: Phytochemicals and Cucurbitane Triterpenoidsmentioning

confidence: 99%

Kuguacin J, a Triterpenoid from Momordica charantia Linn: A Comprehensive Review of Anticarcinogenic Properties

Limtrakul¹,

Pitchakarn²,

Suzuki³

2013

Carcinogenesis

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Inhibitory effect of cucurbitacin E on pancreatic cancer cells growth via STAT3 signaling

Abstract: Our results suggested that cucurbitacin E may be an effective regimen for the chemotherapy of pancreatic cancer.

Cited by 62 publications

References 31 publications

Dietary compounds as potent inhibitors of the signal transducers and activators of transcription (STAT) 3 regulatory network

Dietary compounds as potent inhibitors of the signal transducers and activators of transcription (STAT) 3 regulatory network

In vitroandin vivoanticancer properties of cucurbitacin isolated fromCayaponia racemosa

Kuguacin J, a Triterpenoid from Momordica charantia Linn: A Comprehensive Review of Anticarcinogenic Properties

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