bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1611: EGCG inhibits growth of human pancreatic tumors orthotopically implanted in BALB/c Nude mice through activation of FKHRL1/FOXO3a transcription factor.
Authors: Shankar Sharmila , Marsh Luke , Jackman Chris , Srivastava Rakesh K. 
Published: August 2012

Abstract
The forkhead transcription factors of the O class (FOXO) play a major role in cell proliferation, angiogenesis, metastasis and tumorigenesis. The objectives of this study were to examine whether FKHRL1/FOXO3a modulates antitumor activity of EGCG in pancreatic cancer model in vivo. PANC-1 cells were orthotopically implanted into BALB/c Nude mice and gavaged with EGCG after tumor formation. Cell proliferation and apoptosis were measured by Ki67 and TUNEL staining, respectively. FKHRL1 nuclear translocation, and DNA binding were measured by immunohistochemistry and gelshift assay, respectively. The expression of PI3K, AKT, ERK, and FOXO3a and its target genes were measured by the Western blot analysis. EGCG-treated mice showed significant inhibition in tumor growth which was associated with reduced phosphorylation of ERK, PI3K, AKT, FKHRL1/FOXO3a and expression of FOXO target genes. EGCG induced apoptosis by up-regulating Bim and activating caspase-3. EGCG inhibited markers of cell cycle (p27/KIP1), angiogenesis (CD31, VEGF, IL-6, IL-8 and HIF1α), and metastasis (MMP2 and MMP7). EGCG inhibited epithelial mesenchymal transition by upregulating the expression of E-cadherin and inhibiting the expression of N-cadherin, and Zeb1. These data suggest that EGCG inhibits pancreatic cancer orthotopic tumor growth, angiogenesis and metastasis which are associated with inhibition of PI3K/AKT and ERK pathways resulting in activation of FKHRL1/FOXO3a transcription factor.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1611. doi:1538-7445.AM2012-1611
Abstract 1615: Anthocyanin-rich black raspberry extract negatively regulates stem cell related molecules, EMT, and pluripotency of pancreatic cancer stem cells
Authors: Aravindan Natarajan , Aravindan Sheeja , Herman Terence S. , Natarajan Mohan 
Published: August 2012

Abstract
Ascertaining the potentials of diet-derived phenolics in eradicating cancer stem cells (CSCs), that proliferate and self-renew extensively leading to the initiation and progression of tumor, may escort significant clinical implications. Recently, we have shown that black raspberry extract (RSE) potentiates pancreatic cancer (PC) cell killing by targeting transcriptional machinery. Herein, we investigated ex vivo the effect of RSE on the regulation of EMT, pluripotency maintaining and other stem cell related molecules in PC-CSCs. CD133+CD44+CD24+ESA+ PC-CSCs isolated from human PC xenografts developed in athymic NCr-nu/nu nude mice with human MiaPaCa2, BXPC3, Panc-1 or Panc-3.27 cells were maintained in vitro. PC-CSCs exposed to RSE (2.0μg) for 3h were assessed for transcriptional regulation of 93 stem cell related molecules using QPCR profiling. Expression and cellular localization of epithelial-to-mesenchymal transition (EMT) markers and pluripotent maintaining factors including ABCG2, E-Cadherin, N-Cadherin, MYB, MYC, Nanog and SOX2 in MiaPaCa2, BXPC3 xenografts were assessed using immunohistochemistry (IHC). The results revealed that RSE significantly inhibited 83, 50 and 54 stem cell related molecules in PC-CSCs isolated from xenografts developed using MiaPaCa2, Panc-1 and Panc 3.27 respectively. Of these, 27 genes were commonly suppressed by RSE in all three PC-CSCs population. Further, IHC staining showed complete repression of EMT and pluripotent markers in both MiaPaCa2 and BXPC3 xenografts. Together, these data imply that RSE may exert selective inhibition of EMT and pancreatic CSCs’ self renewal capacity and, may thus serve as a potential “deliverable” to negate PC initiation and progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1615. doi:1538-7445.AM2012-1615
Abstract 1616: Preventive effects of EGCG on diethylnitrosamine-induced liver tumorigenesis in obese and diabetic C57BL/KsJ-db/db mice
Authors: Kochi Takahiro , Shimizu Masahito , Sakai Hiroyasu , Shirakami Yohei , Kubota Masaya , Tanaka Takuji , Moriwaki Hisataka 
Published: August 2012

Abstract
Background and aims: Obesity and related metabolic abnormalities, including insulin resistance and a state of chronic inflammation, increase the risk of hepatocellular carcinoma (HCC). Abnormal activation of the IGF/IGF-1R axis is also involved in obesity-related liver tumorigenesis. In the present study, we examined the effects of (-)-epigallocatechin gallate (EGCG), a major biologically active component of green tea, on the development of diethylnitrosamine (DEN)-induced liver tumorigenesis in C57BL/KsJ-db/db (db/db) obese mice. Methods: Male db/db mice were given tap water containing 40 ppm DEN for 2 weeks and then they received drinking water containing 0.1% EGCG for 34 weeks. Results: At sacrifice, drinking water with EGCG significantly inhibited the development of liver cell adenomas in comparison to the control EGCG-untreated group. EGCG inhibited the phosphorylation of the IGF-1R, ERK, Akt, GSK-3β, Stat3, and JNK proteins in the livers of experimental mice. The serum levels of insulin, IGF-1, IGF-2, free fatty acid, and TNF-α were all decreased by drinking EGCG. EGCG also decreased the expression of TNF-α, IL-6, IL-1α, and IL-18 mRNAs in the livers. In addition, EGCG improved liver steatosis and activated the AMPK protein in the liver. Conclusion: EGCG prevents obesity-related liver tumorigenesis by inhibiting the IGF/IGF-1R axis, improving hyperinsulinemia, and attenuating chronic inflammation. EGCG, therefore, may be useful in the chemoprevention of liver tumorigenesis in obese individuals.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1616. doi:1538-7445.AM2012-1616
Abstract 1617: Erianin induces apoptosis of human hepatocellular carcinoma HepG2 cells
Authors: Wang Jing , An Junxia , Zhu Qiyu , Luo Liping , Ma Yuling , Tang Yaxiong 
Published: August 2012

Abstract
Novel effective drugs are still urgently needed in the prevention and treatment of Hepatocellular carcinoma (HCC). Erianin, a natural product isolated from Dendrobium chrysotoxum Lindl., is often used as an anti-pyretic and an analgesic in traditional Chinese medicine. Herein, we have assesed the antitumor potential and molecular mechanisms of erianin on the Hepatocellular carcinoma HepG2 cancer cells in vitro. The results shows that erianin could significantly inhibit the cell proliferation of HepG2 cells in dose- and time- dependent manners that were associated with induced apoptosis and cell cycle G2-M arrest. The IC50 of erianin for 48 h was estimated to be 11.4 nmol/L. Mechanistically, erianin could induce the release of cytochrome c from mitochondria into the cytosol, and activate the cleavage of Caspase-9, -7, -3 and eventually the PARP in a dose-dependent manner, leading to marked apoptotic effect of HepG2 cells. The apoptotic action of erianian was associated with the increased expression of proapoptotic proteins: Bax, Bad, Bik and PUMA and decreased expression of Mcl-1 and Survivin. Taken together, these results suggest the potential usefulness of erianin for prevention and treatment of HCC. References 1. Gomaa AI, Khan SA, Toledano MB, Waked I, Taylor-Robinson SD. Hepatocellular carcinoma: epidemiology, risk factors and pathogenesis. World J Gastroenterol, 2008, 14 2. 2. Tang Y, Simoneau AR, Xie J, Shahandeh B, Zi X. Effects of the Kava Chalcone Flavokawain A Differ in Bladder Cancer Cells with Wild-type versus Mutant p53. Cancer Prevention Research 2008, 1(6):439-51. 3. Tang Y, Simoneau AR, Liao W, Guo Y, Hoang BH, Hope C, Liu F, Li S, Xie J, Holcombe RF, Jurnak FA, Mercola D, Zi X. WIF1, a Wnt pathway inhibitor, regulates SKP2 and c-myc expression leading to G1 arrest and growth inhibition of human invasive urinary bladder cancer cells. Molecular Cancer Therapeutics 2009, 8(2): 458-68.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1617. doi:1538-7445.AM2012-1617
Abstract 1622: Possible role of visfatin in hepatoma progression and the effects of branched-chain amino acids on visfatin-induced proliferation in human hepatoma cells
Authors: Shimizu Masahito , Ninomiya Soranobu , Moriwaki Hisataka 
Published: August 2012

Abstract
Obesity and related metabolic abnormalities, including adipocytokine dysbalance, are risk factors for hepatocellular carcinoma (HCC). Visfatin, an adipocytokine that is highly expressed in visceral fat, is suggested to play a role in the progression of human malignancies. Branched-chain amino acids (BCAA) reduces the incidence of HCC in obese patients with liver cirrhosis and prevents obesity-related liver carcinogenesis in mice. In this study, we investigated the possible role of visfatin on HCC progression and the effects of BCAA on visfatin-induced proliferation of HCC cells. In patients with HCC, serum visfatin levels were significantly correlated with stage progression and tumor enlargement. Visfatin preferentially stimulated the proliferation of HepG2, Hep3B, and HuH7 human HCC cells compared with Hc normal hepatocytes. Visfatin phosphorylated ERK, Akt, and GSK-3β proteins in HepG2 cells. LY294002 (a PI3K inhibitor), PD98059 (a MEK1 inhibitor), CHIR99021 (a GSK-3β inhibitor), and BCAA significantly inhibited visfatin-induced proliferation in HepG2 cells. BCAA also inhibited phosphorylation of GSK-3β, increased cellular levels of p21, caused cell cycle arrest in G0-G1, and induced apoptosis in HCC cells in the presence of visfatin. These findings suggest that visfatin plays a critical role in the proliferation of HCC cells and may be associated with the progression of this malignancy. In addition, BCAA might inhibit obesity-related liver carcinogenesis by targeting and, possibly, by overcoming the stimulatory effects of visfatin.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1622. doi:1538-7445.AM2012-1622
Abstract 1625: Curcumin induces expression of 15-hydroxyprostaglandin dehydrogenase in normal gastric mucosa RGM-1 cells: Possible involvement of AP-1
Authors: Jang Ji-Hye , Park Jong-Min , Woo Jeonghwa , Lee Young Wook , Surh Young-Joon , Na Hye-Kyung 
Published: August 2012

Abstract
Overproduction of prostaglandin E2 (PGE2) has been reported to be implicated in carcinogenesis. The intracellular level of PGE2 is regulated not only by its biosynthesis, but also by the degradation process. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is the key enzyme that catalyzes the first step in the inactivation of PGE2. In the present study, we found that curcumin, a yellow coloring agent present in the rhizome of Curcuma longa Linn (Zingiberaceae), induced expression of 15-PGDH in normal rat gastric mucosa cells (RGM-1) in a concentration and time dependent manners. The mRNA level of 15-PGDH was also increased by curcumin treatment. By using deletion constructs of 15-PGDH promoter, we found that activator protein-1 (AP-1) is the most essential transcription factor responsible for curcumin-induced upregulation of 15-PGDH expression. Curcumin induced phosphorylation of ERK1/2 and JNK1/2, but did not affect activation of p38 MAP kinase. However, treatment with U0126 and SP600125, pharmacological inhibitors of ERK and JNK, respectively failed to suppress the induction of 15-PGDH expression in curcumin-treated RGM-1 cells. Curcumin enhanced the expression of c-Jun, c-Fos and CREB in the nuclear fraction of RGM-1 cells. In contrast, tetrahydrocurcumin which lacks the α,β-unsaturated carbonyl group failed to induce expression 15-PGDH, suggesting that the electrophilic α,β-unsaturated carbonyl group of curcumin plays a critical role in its induction of 15-PGDH expression in RGM-1 cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1625. doi:1538-7445.AM2012-1625
Abstract 1626: Honokiol inhibits IL-8 production and exerts anti-tumor effects in colon cancer cells: therapeutic and preventive implications
Authors: Arora Sumit , Srivastava Sanjeev K. , Bhardwaj Arun , Singh Ajay P. , Piazza Gary A. , Owen Laurie B. , Singh Seema 
Published: August 2012

Abstract
Interleukin-8 (IL-8), a member of CXC subfamily of chemokines, plays important roles in inflammation and cancer. The biological action of IL-8 is mediated through binding to its receptors, CXCR1 (IL-8RA) and CXCR2 (IL-8RB), which are members of the seven transmembrane G-protein-coupled receptor family. Overexpression of IL-8 has been detected in many human tumors, including colon cancer, and it is a major component of the inflammatory tumor microenvironment. Functional studies have shown that IL-8 acts as an autocrine/paracrine growth factor, and promotes growth, invasion, metastasis, angiogenesis and chemoresistance in colon cancer, implying that it could serve as a preventive and therapeutic target. In this study, we examined the effect of honokiol, a biologically active biphenolic compound isolated from the oriental medicinal plant Magnolia officinalis/grandiflora, on two colon cancer cells lines, SW620 and HCT116. Both the cell lines are highly tumorigenic and metastatic, and express high levels of IL-8. Our data demonstrated that honokiol inhibited the expression of IL-8 in both colon cancer cell lines in a dose-dependent manner. IL-8 downregulation by honokiol was also correlated with decreased activation of its transcriptional regulator NF-κB. Honokiol treatment enhanced cytoplasmic accumulation of NF-κB with a concomitant decrease in the nuclear fraction and reduced transcriptional activity of NF-κB-responsive promoter. This was associated with decreased phosphorylation of inhibitor of kappa B alpha (IαB-α) leading to its stabilization and enhanced cytoplasmic levels. In addition, honokiol exerted growth inhibitory effects by inducing apoptosis and G1 phase cell cycle arrest. Altogether, these findings suggest that honokiol could serve as a novel preventive and therapeutic agent in colon cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1626. doi:1538-7445.AM2012-1626
Abstract 1628: Tumor suppressor gene demethylation and reactivation in human colon cancer cells by black raspberry anthocyanins
Authors: Kuo Chieh-Ti , Seguin Claire , Stoner Kristen , Cho Seung-Ju , Weng Yui , Tichelaar Jay , Huang Yi-Wen , Huang Tim , Stoner Gary , Wang Li-Shu 
Published: August 2012

Abstract
Our laboratory has shown that the anthocyanins (ACs) in black raspberries (BRBs) are responsible for much of their chemopreventive effects in the rat esophagus. The present study was undertaken to determine the effects of BRB ACs on human colon cancer cells in vitro. Three days of AC treatment at 5 and 25 μg/ml medium significantly decreased cell proliferation and increased apoptosis in HCT116, Caco2, and SW480 human colon cancer cell lines. The ACs also reduced the activities and protein expression levels of DNA methyltransferases 1 and 3 (DNMT1, DNMT3) in all three cell lines. Promoter methylation of p16 (CDKN2A) and the Wnt pathway inhibitors, Sfrp2, Sfrp5 and Wif1, was decreased by AC treatment resulting in increased mRNA expression levels of all three Wnt inhibitors. ACs did not alter global methylation LINE-1. DNMT1 and DNMT3B knockout (KO) HCT116 cells were generated using siRNA to determine the role of these methyltransferases in AC-induced demethylation. In DNMT1 KO cells, the promoter methylation of Sfrp5 was reduced when compared with wild type HCT116 cells. AC treatment further reduced promoter methylation of Sfrp5 in DNMT1 KO cells suggesting that the ACs targeted protein(s) other than DNMT1 to regulate methylation. Promoter methylation of Sfrp5 was decreased to almost zero by treatment of DNMT3B KO cells with ACs. Interestingly, promoter methylation of p16 was reduced in both DNMT1 and DNMT3B KO cells, and AC treatment further reduced p16 methylation in both lines. In conclusion, these results suggest that ACs demethylated and reactivated tumor suppressor genes through regulation of DNMT1 and DNMT3B. This research was supported by NCI grant CA148818.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1628. doi:1538-7445.AM2012-1628
Abstract 1630: Vitamin E delta-tocotrienol prevents azoxymethane-induced colon carcinogenesis progression in Fisher-344 rats
Authors: Pimiento Jose M. 
Published: August 2012

Abstract
Background: Chemoprevention by bioactive food components has emerged as an alternative approach for the prevention of colorectal carcinogenesis. We have shown that natural vitamin E delta-tocotrienol is the most bioactive tocotrienol against pancreatic cancer. This study evaluated the efficacy of vitamin E delta-tocotrienol feeding in the prevention of azoxymethane-induced colorectal polyps and cancer formation in Fisher-344 rats. We also evaluated the antitumor activity of vitamin E delta-tocotrienol in colorectal cancer cell lines and in APCmin mouse model. Methods: The in vivo antitumor activity of delta-tocotrienol was evaluated in azoxymethane-treated Fisher-344 rats. Rats were administered azoxymethane (15 mg/kg, SC, 2 x in 2 weeks) then randomly selected into 3 groups: 1) No treatment, 2) Vehicle (ethanol extracted olive oil, 1 ml/kg, PO twice daily and 3) Delta-tocotrienol (200 mg/kg, PO) twice daily for 20 or 40 weeks. The animals were euthanized and the colons were examined for polyps and cancers. Colon tissues were fixed in buffered formalin, embedded, cut and stained with H & E and scored. The APCmin mice were treated with 1) vehicle (olive oil, 1 ml/kg, PO) twice daily for 2 weeks and 2) Delta-tocotrienol (200 mg/kg, PO) twice daily for 2 weeks. Mice euthanized and colon tissues isolated and evaluated for proliferation and apoptosis by immunohistochemistry staining. The in vitro anti-tumor activity of delta-tocotrienol was preformed in human colorectal cancer cell lines HCT-116, HT-29 and SW 480. Results: Delta-tocotrienol feeding to azoxymethane-treated rats significantly reduced (75%, p&lt;0.002) the number of polyps formation compared to untreated or vehicle treated rats. Moreover, the number of colon cancer formation was reduced (70%, p&lt;0.001) with delta-tocotrienol feeding compared to untreated or vehicle treated rats. In colonic tissues of APCmin mice, delta-tocotrienol feeding decreased proliferation (Ki-67), induction of p27, and induction of apoptosis (caspase-3) compared to vehicle treated mice. Delta-tocotrienol also inhibited cell proliferation and induced apoptosis in HCT-116, HT-29 and SW 480 cell lines, through induction of nuclear factor kappa-B (NF-kB) and degradation of beta-catenin. Conclusion: These data show the efficacy of natural vitamin E delta-tocotrienol against the early stages of colorectal carcinogenesis as well as anti-proliferative and apoptotic activity in colorectal cancer both in vitro and in vivo. Delta tocotrienol likely targets NF-kB and beta-catenin signaling pathways, suggesting its potential clinical usefulness for the prevention of human colorectal cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1630. doi:1538-7445.AM2012-1630
Abstract 1631: Protection of colon carcinogenesis by estrogen receptor-beta may involve regulation of angiogenesis and invasion specific signaling molecules
Authors: Saleiro Diana , Murillo Genoveva , Hawthorne Michael , Mehta Rajendra 
Published: August 2012

Abstract
Estrogen receptor-beta (ERα) has been suggested to exert anti-tumorigenic effects in the colon. However, its mechanism of action in colon cancer remains unclear. Previously, we demonstrated that azoxymethane (AOM) treated ERα knockout (≥ERKO) mice showed a significantly higher incidence of colonic precancerous lesions compared to AOM-treated WT mice. These results were associated with a decrease in apoptosis and loss of crypt organization in the colonic epithelium of αERKO mice. In the present study, we investigated whether ERα deficiency would also correlate with a higher incidence of colonic tumors. For this, αERKO and WT mice were injected subcutaneously with AOM (10mg/kg) once a week, for six weeks. Forty weeks after the beginning of the study, mice were sacrificed and colonic sections were collected for histopathology, RNA, and protein expression analysis. Evaluation of hematoxylin and eosin sections from each group showed that αERKO mice developed higher number of colonic adenomas (1.40 ± 0.40) than WT mice (0.33 ± 0.21) (p &lt; 0.05). Furthermore, Mouse Cancer PathwayFinder Superarray revealed a greater than two-fold increase of angiogenesis and invasion specific signaling molecules in ERα-deficient tumors compared to WT ones. These findings highlight the importance of ERα against colon carcinogenesis progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1631. doi:1538-7445.AM2012-1631