β-Escin inhibits colonic aberrant crypt foci formation in rats and regulates the cell cycle growth by inducing p21waf1/cip1 in colon cancer cells

Patlolla, Jagan Mohan R.; Raju, Jayadev; Swamy, Malisetty V.; Rao, Chinthalapally V.

doi:10.1158/1535-7163.mct-05-0495

Cited by 78 publications

(67 citation statements)

References 44 publications

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“…p21 Cip1/Waf1 has been shown to regulate cell cycle progression in both G1 and G2 phases through p53-dependent or p53-independent pathways (Niculescu, Chen et al 1998). Consistent with the findings of previous research (Patlolla, Raju et al 2006), neither DU-145 nor PC-3 cell lines expressed functional p53 (Fan, Kumaravel et al 2004) in the present study , suggesting that p53 may not play an essential role in escin-induced apoptosis or conventional chemotherapeutic agents is mediated by p53 (Brown and Wouters 1999), the p53-independent activation of p21 WAF1/CIP1 triggered by escin treatment can represent an alternative therapeutic approach for prostate cancer patients who fail to respond to conventional agents targeting p53 . inactive.…”

Section: Escin Induces Cell Cycle Arrest At G2/m Phase and Modulates supporting

confidence: 89%

“…The retinoblastoma (Rb) tumor suppressor gene product phosphorylated-Rb (pRb) serves as a downstream mediator of p21 (Schafer 1998) and plays a crucial role in cell cycle control. Patlolla et al (Patlolla, Raju et al 2006) report that pRb is inhibited by escin. Qiu et al (Qiu, Schönthal et al 1998) demonstrate that the loss of functional pRb leads to G2/M arrest following p21 induction in the human osteosarcoma cell line Saos-2 .…”

Section: Escin Induces Cell Cycle Arrest At G2/m Phase and Modulates mentioning

confidence: 98%

“…The horse chestnut grows in Iran, Northern India, Asia Minor, South-East Europe, America, from the Balkans to the Caucasus, as well as in the Korea (Fournier 1948). Escin is a natural mixture of triterpene saponins ( Figure 6) (Costantini 1999) and cell cycle arrest (Patlolla, Raju et al 2006, Harikumar, Sung et al 2010, Tan, Li et al 2010, Zhang, Gao et al 2011, no study has addressed these functions in human prostate cancer cells.…”

Section: Figure 3 Typical Recurrent Prostate Cancer Outcomementioning

confidence: 99%

See 2 more Smart Citations

Cytotoxic Effects of Escin on Human Castration-resistant Prostate Cancer Cells Through the Induction of Apoptosis and G2/M Cell Cycle Arrest

Piao

Kang

Lee

et al. 2014

Urology

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Section: Escin Induces Cell Cycle Arrest At G2/m Phase and Modulates supporting

confidence: 89%

Section: Escin Induces Cell Cycle Arrest At G2/m Phase and Modulates mentioning

confidence: 98%

Section: Figure 3 Typical Recurrent Prostate Cancer Outcomementioning

confidence: 99%

See 1 more Smart Citation

Cytotoxic Effects of Escin on Human Castration-resistant Prostate Cancer Cells Through the Induction of Apoptosis and G2/M Cell Cycle Arrest

Piao

Kang

Lee

et al. 2014

Urology

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“…The pentacyclic triterpenoid b-escin was recently found to exhibit significant antitumor effects in human hepatocellular carcinoma both in vitro and in vivo (Zhou et al 2009). In addition, this effect of b-escin has also been reported to suppress colonic aberrant crypt foci formation in rats and to inhibit growth of colon cancer cells (Patlolla et al 2006). On the other hand, diosgenin and butein were shown to inhibit P-STAT3 through the induction of phosphatases.…”

Section: Hepatocellular Carcinomamentioning

confidence: 96%

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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“…b-Escin has been used widely to treat chronic venous insufficiency (4), hemorrhoids, and postoperative edema resulting from surgery (5). Studies from our laboratory showed that b-escin inhibits the growth of colon cancer cells and inhibits chemically induced colon carcinogenesis in rats (6). In recent years, several studies have shown that b-escin possesses anticancer activity by inhibiting growth and inducing apoptosis in various human cancer cell lines derived from lung (7), pancreatic (8), and liver (9) cancers and in leukemia and multiple myeloma (10).…”

Section: Introductionmentioning

confidence: 99%

β-Escin Inhibits NNK-Induced Lung Adenocarcinoma and ALDH1A1 and RhoA/Rock Expression in A/J Mice and Growth of H460 Human Lung Cancer Cells

Patlolla

Biddick

et al. 2013

Cancer Prevention Research

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Lung cancer is the leading cause of cancer-related deaths. b-Escin, a triterpene saponin isolated from horse chestnut seeds, was tested for inhibition of lung adenoma and adenocarcinoma induced by the tobacco carcinogen 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in female A/J mice; and its possible mode of action was evaluated using the H460 human lung cancer cell line. At 6 weeks of age, 35 mice were fed AIN-76A-modified diet, and one week later, lung tumors were induced with a single intraperitoneal (i.p.) injection of 10 mmol NNK/mouse. Three weeks after the NNK treatment, groups of mice were fed either control or experimental diets containing 500 ppm for 20 weeks (10 control, 5 b-escin) or 36 weeks (15 control, 5 b-escin) and evaluated for lung tumor via histopathologic methods. Administration of 500 ppm b-escin significantly suppressed lung tumor (adenoma þ adenocarcinoma) formation by more than 40% (P < 0.0015) at 20 weeks and by 53.3% (P < 0.0001) at 37 weeks. b-Escin inhibited NNK-induced lung adenocarcinoma formation by 65% (P < 0.001) at 20 weeks and by 53% (P < 0.0001) at 37 weeks. Immunohistochemical analysis revealed that lung tumors from mice exposed to b-escin showed significantly reduced aldehyde dehydrogenase (ALDH)1A1 and phospho-Akt (p-Akt) expression when compared with those in mice fed control diet. Aldefluor assay for ALDH revealed that among H460 lung cancer cells treated with different concentrations of b-escin (0-40 mmol/L), the subpopulation of cells with elevated ALDH activity was inhibited significantly. Our findings suggest that b-escin inhibits tobacco carcinogeninduced lung tumor formation by modulating ALDH1A1-positive cells and RhoA/Rock signaling. Cancer Prev Res; 6(10);

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β-Escin inhibits colonic aberrant crypt foci formation in rats and regulates the cell cycle growth by inducing p21waf1/cip1 in colon cancer cells

Cited by 78 publications

References 44 publications

Cytotoxic Effects of Escin on Human Castration-resistant Prostate Cancer Cells Through the Induction of Apoptosis and G2/M Cell Cycle Arrest

Cytotoxic Effects of Escin on Human Castration-resistant Prostate Cancer Cells Through the Induction of Apoptosis and G2/M Cell Cycle Arrest

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

β-Escin Inhibits NNK-Induced Lung Adenocarcinoma and ALDH1A1 and RhoA/Rock Expression in A/J Mice and Growth of H460 Human Lung Cancer Cells

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