Cancer Letters RSS feed: Current Issue. CANCER LETTERS is a journal providing rapid publication of full-length articles in the broad area of cancer research. The journal places emphasis on the molecular and cell biology of cancer, oncogenes, carcinogenesis, radiation biology, molecular pathology, hormones and cancer, viral oncology, biology of cancer and metastasis, molecular cytogenetics, epidemiology; and experimental therapeutics. The primary criterion for publication is interest to a multidisciplinary audience. Papers should be technically sound and substantiated by sufficient experimental detail. Clinical papers will be accepted if they contribute to the understanding of the basic mechanisms underlying disease. Cancer Letters now offers online submission for authors. Please submit manuscripts at http://www.ees.elsevier.com/can and follow the instructions on the site.http://www.cancerletters.info/?rss=yesElsevier Inc.en © 2010 Published by Elsevier Inc. All rights reserved. Cancer Letters0304-383529711 November 2010 © 2010 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.cancerletters.info/article/PIIS0304383510004027/abstract?rss=yesEditorial Board10.1016/S0304-3835(10)00402-7Cancer Letters 297, 1 (2010)2010-11-01Cancer Letters2010-11-012971S0304-3835(10)X0020-9iiiihttp://www.cancerletters.info/article/PIIS0304383510002338/abstract?rss=yesAbstract: Curcumin from the rhizome of theCurcuma longa plant has chemopreventative activity and inhibits the growth of neoplastic cells. Since p53 has been suggested to be important for anticancer activity by curcumin, we investigated curcumin-induced cytotoxicity in cultures of p53+/+ and p53−/− HCT-116 colon cancer cells, as well as mutant p53 HT-29 colon cancer cells. Curcumin killed wild-type p53 HCT-116 cells and mutant p53 HT-29 cells in a dose- and time-dependent manner. In addition, curcumin-treated p53+/+ HCT-116 cells and mutant p53 HT-29 cells showed upregulation of total and activated p53, as well as increased expression of p53-regulated p21, PUMA (p53 upregulated modulator of apoptosis), and Bax; however, an equivalent cytotoxic effect by curcumin was observed in p53+/+ and p53−/− HCT-116 cells, demonstrating that curcumin-induced cytotoxicity was independent of p53 status. Similar results were obtained when the cytotoxic effect of curcumin was assessed in wild-type p53 HCT-116 cells after siRNA-mediated p53 knockdown. Chromatin condensation, poly (ADP-ribose) polymerase-1 cleavage and reduced pro-caspase-3 levels in curcumin-treated p53+/+ and p53−/− HCT-116 cells suggested that curcumin caused apoptosis. In addition, exposure to curcumin resulted in superoxide anion production and phosphorylation of oxidative stress proteins in p53+/+ and p53−/− HCT-116 cells. Collectively, our results indicate that, despite p53 upregulation and activation, curcumin-induced apoptosis in colon cancer cells was independent of p53 status and involved oxidative stress. Curcumin may therefore have therapeutic potential in the management of colon cancer, especially in tumorsthatare resistant to conventional chemotherapydue todefects inp53 expression or function.Curcumin causes superoxide anion production and p53-independent apoptosis in human colon cancer cellsJane L. Watson, Richard Hill, Paul B. Yaffe, Anna Greenshields, Mark Walsh, Patrick W. Lee, Carman A. Giacomantonio, David W. Hoskin10.1016/j.canlet.2010.04.018Cancer Letters 297, 1 (2010)2010-05-17Cancer Letters2010-05-172971S0304-3835(10)X0020-9Original Articles18http://www.cancerletters.info/article/PIIS030438351000234X/abstract?rss=yesAbstract: Previous studies in our laboratory have suggested that gankyrin expression is correlated with a malignant phenotype in colorectal cancer. Here, we investigated the possible role of gankyrin in pancreatic carcinogenesis. Gankyrin expression was significantly increased in pancreatic cancer compared to non-cancerous tissues. This expression significantly enhanced cancer cell proliferation and growth in vitro and in vivo. Suppression of gankyrin downregulated cyclin A, cyclin D1, cyclin E, CDK2, CDK4, PCNA and p-Rb but upregulated p27, Rb and p53. However, gankyrin overexpression led to opposite results. Thus, gankyrin could enhance pancreatic cancer cell proliferation by promoting cell cycle progression and p53 degradation.Gankyrin promotes the proliferation of human pancreatic cancerYun Meng, Lijie He, Xuegang Guo, Shanhong Tang, Xiaodi Zhao, Rui Du, Jiang Jin, Qian Bi, Hao Li, Yongzhan Nie, Jie liu, Daiming Fan10.1016/j.canlet.2010.04.019Cancer Letters 297, 1 (2010)2010-05-19Cancer Letters2010-05-192971S0304-3835(10)X0020-9Original Articles917http://www.cancerletters.info/article/PIIS0304383510002351/abstract?rss=yesAbstract: A novel compound, acetyltanshinone IIA (ATA) was obtained from chemical modifications of tanshinone TIIA (TIIA) isolated from a medicinal plant, Salvia miltiorrhiza. ATA exhibited increased water solubility and stronger apoptotic activity on multiple cancer cell lines than TIIA. ATA displayed a higher growth inhibition ability on breast cancer especially HER2 positive cells than normal cells and it inhibited xenografted tumor growth in mice. Mechanistic studies showed that ATA could induce significant reactive oxygen species (ROS) generation, Bax translocation to mitochondria, resulting in mitochondria damage, cytochrome c release, caspase-3 activation and apoptotic cell death. ATA-mediated ROS production and its downstream apoptotic events could be blocked by an antioxidant agent, propyl gallate, indicating the prominent role of ROS in ATA-induced apoptosis. Overexpression of Bcl-2 protein reduced ATA-induced cell death. In conclusion, ATA is a novel anticancer agent with potent in vitro and in vivo anticancer ability. ROS-mediated Bax activation should be the mechanism by which ATA induces apoptosis and inhibits tumor growth.A novel compound modified from tanshinone inhibits tumor growth in vivo via activation of the intrinsic apoptotic pathwayHong-Lei Tian, Ting Yu, Nai-Ning Xu, Chao Feng, Li-Ying Zhou, Hou-Wei Luo, Donald C. Chang, Xiao-Feng Le, Kathy Qian Luo10.1016/j.canlet.2010.04.020Cancer Letters 297, 1 (2010)2010-05-24Cancer Letters2010-05-242971S0304-3835(10)X0020-9Original Articles1830http://www.cancerletters.info/article/PIIS0304383510002363/abstract?rss=yesAbstract: Medullary thyroid carcinoma (MTC) is a multiple endocrine neoplasia type 2 syndrome caused by mutations in extracellular receptor or intracellular kinase domains of the RET proto-oncogene. Activation of the Ras/Raf/MEK/ERK pathway can lead to growth arrest by secreting leukemia inhibitory factor (LIF) in MTC cells harboring a RET receptor domain mutation. Here, we report that Ras/Raf/MEK/ERK can also mediate, via LIF, growth inhibition in MTC cells harboring a RET kinase domain mutation. Ras/Raf/MEK/ERK activation was sufficient to induce growth inhibition and LIF expression in the human MTC line MZ-CRC-1. Presence of LIF-mediated signaling was determined by blocking the activity of culture medium conditioned by Raf-activated cells using anti-LIF neutralizing antibody. In addition, recombinant LIF effectively suppressed cell proliferation via cell cycle arrest in G0/G1 phase. Expression of dominant negative STAT3 abrogated LIF effects, indicating that LIF mediates its signaling through the JAK/STAT3 pathway. These results suggest that growth inhibition and activation of the autocrine/paracrine signaling through LIF/JAK/STAT may be a common response to Ras/Raf activation in different MTC types, and justify further evaluation of LIF as a potential anticancer agent for MTC.Leukemia inhibitory factor can mediate Ras/Raf/MEK/ERK-induced growth inhibitory signaling in medullary thyroid cancer cellsDumrongkiet Arthan, Seung-Keun Hong, Jong-In Park10.1016/j.canlet.2010.04.021Cancer Letters 297, 1 (2010)2010-05-31Cancer Letters2010-05-312971S0304-3835(10)X0020-9Original Articles3141http://www.cancerletters.info/article/PIIS0304383510002375/abstract?rss=yesAbstract: Baicalein is a widely used Chinese herbal medicine that has been used historically in anti-inflammatory and anti-cancer therapy. However, the molecular mechanism of its anti-cancer activity remains poorly understood and warrants further investigations. The purpose of this study is to verify the activity of baicalein to inhibit the invasion of MDA-MB-231 human breast cancer cells. The results indicated that baicalein suppressed MDA-MB-231 cell adhesion to fibronectin-coated substrate, wound healing migration and invasion through the Matrigel in a concentration-dependent manner. Western blot and gelatin zymography analysis showed that baicalein significantly inhibited the expression and secretion of matrix metalloproteinases 2/9 (MMP-2/9) in MDA-MB-231 cells. Additionally, treatment of MDA-MB-231 cells with baicalein down-regulated the expression of MMP-2/9 involved mitogen-activated protein kinases (MAPK) signaling pathway. Taken together, baicalein had potential to suppress the adhesion, migration and invasion of MDA-MB-231 cancer cells in vitro and it could serve as a promising drug for the treatment of cancer metastasis.Flavonoid baicalein suppresses adhesion, migration and invasion of MDA-MB-231 human breast cancer cellsLing Wang, Yun Ling, Yan Chen, Cheng-Ling Li, Feng Feng, Qi-Dong You, Na Lu, Qing-Long Guo10.1016/j.canlet.2010.04.022Cancer Letters 297, 1 (2010)2010-05-26Cancer Letters2010-05-262971S0304-3835(10)X0020-9Original Articles4248http://www.cancerletters.info/article/PIIS0304383510002387/abstract?rss=yesAbstract: The roles of transient receptor potential (TRP) cation channels in pancreatic tumorigenesis are essentially unknown. Here, we focus on the TRP melastatin-subfamily (TRPM) members. Expression of the thermally regulated transmembrane Ca2+-permeable channel TRPM8 is consistently up-regulated in human pancreatic adenocarcinoma cell lines and tissues. TRPM8-deficient pancreatic cancer cells have reduced ability of proliferation and cell cycle progression with elevated levels of cyclin-dependent kinase inhibitors. These results indicate that TRPM8 is aberrantly over-expressed in pancreatic adenocarcinoma and required for cellular proliferation, and they support further investigation of the potential of TRPM8 as a clinical biomarker and therapeutic target in pancreatic adenocarcinoma.Transient receptor potential channel TRPM8 is over-expressed and required for cellular proliferation in pancreatic adenocarcinomaNelson S. Yee, Weiqiang Zhou, Minsun Lee10.1016/j.canlet.2010.04.023Cancer Letters 297, 1 (2010)2010-06-02Cancer Letters2010-06-022971S0304-3835(10)X0020-9Original Articles4955http://www.cancerletters.info/article/PIIS0304383510002399/abstract?rss=yesAbstract: Application of camptothecin (CPT) is hampered due to its extreme water insolubility and unpredictable side effects. Therefore, it is essential to establish an efficient and safe protocol for the administration of camptothecin against tumor growth and metastasis. Here, we encapsulated camptothecin with N-trimethyl chitosan (CPT–TMC) and tested it on BALB/c mice subcutaneously injected with murine hepatocellular carcinoma cells at the hindlimb feet pad. CPT–TMC effectively inhibited tumor growth and lymphatic metastasis, prolonged survival time, yet without apparent toxic effects. Thus, CPT–TMC may provide a novel and effective therapeutic strategy against human advanced hepatic cancer without conspicuous systemic toxic effects.In vivo antitumor and antimetastatic activities of camptothecin encapsulated with N-trimethyl chitosan in a preclinical mouse model of liver cancerLina Zhou, Xingyi Li, Xiancheng Chen, Zhiyong Li, Xianping Liu, Shengtao Zhou, Qian Zhong, Tao Yi, Yuquan Wei, Xia Zhao, Zhiyong Qian10.1016/j.canlet.2010.04.024Cancer Letters 297, 1 (2010)2010-05-24Cancer Letters2010-05-242971S0304-3835(10)X0020-9Original Articles5664http://www.cancerletters.info/article/PIIS0304383510002417/abstract?rss=yesAbstract: Nuclear retinoid X receptors (RXRs) and peroxisome proliferator-activated receptors (PPARs are potential candidates as drug target for cancer prevention and treatment. We investigated if the rexinoid 6-OH-11-O-hydroxyphenantrene (IIF) potentiates the antitumoral properties of PPARγ ligands as ciglitazone and pioglitazone, on two colon cancer cell lines: HCA-7 and HCT-116. Drugs inhibited cell growth and induced apoptosis synergistically. The combination resulted in a decrease of cyclooxigenase-2, metalloproteinases-2 and -9 expression level and activity while PPARγ, RXRγ and tissue inhibitors of metalloproteinase-1 and -2 expression were increased. Finally, IIF potentiated PPAR transcriptional activity by enhancement of peroxisome proliferator response elements transactivation.RXRγ and PPARγ ligands in combination to inhibit proliferation and invasiveness in colon cancer cellsAlessio Papi, Paola Rocchi, Anna Maria Ferreri, Marina Orlandi10.1016/j.canlet.2010.04.026Cancer Letters 297, 1 (2010)2010-06-01Cancer Letters2010-06-012971S0304-3835(10)X0020-9Original Articles6574http://www.cancerletters.info/article/PIIS030438351000251X/abstract?rss=yesAbstract: We examined the effect of hypoxia on apoptosis of human colorectal cancer (CRC) cells in vitro and in vivo. All cell lines tested were susceptible to hypoxia-induced apoptosis. DCA treatment caused significant apoptosis under normoxia in SW480 and Caco-2 cells, but these cells displayed decreased apoptosis when treated with DCA combined with hypoxia, possibly through HIF-1α dependent pathways. DCA treatment also induced significantly increased growth of SW480 tumor xenografts, and a decrease in TUNEL positive nuclei in hypoxic but not normoxic regions of treated tumors. Thus DCA is cytoprotective to some CRC cells under hypoxic conditions, highlighting the need for further investigation before DCA can be used as a reliable apoptosis-inducing agent in cancer therapy.Sodium dichloroacetate (DCA) reduces apoptosis in colorectal tumor hypoxiaSiranoush Shahrzad, Kristen Lacombe, Una Adamcic, Kanwal Minhas, Brenda L. Coomber10.1016/j.canlet.2010.04.027Cancer Letters 297, 1 (2010)2010-05-31Cancer Letters2010-05-312971S0304-3835(10)X0020-9Original Articles7583http://www.cancerletters.info/article/PIIS0304383510002521/abstract?rss=yesAbstract: Lentiviral vector containing the HSV1-tk and firefly luciferase (fLuc) gene was infected into C6 and C6-TL expressing HSV1-tk and fLuc gene was generated. C6-TL showed higher [125I]IVDU uptake than C6. The survival rate of C6-TL decreased more rapidly with increasing GCV dose and was well correlated with fLuc activity. The images of microPET clearly demonstrated higher uptake of [18F]FHBG into the C6-TL tumor. Inhibition of tumor growth was observed in C6-TL tumor-bearing mice treated with GCV through tumor size measurement and bioluminescence imaging. The therapeutic effect of HSV1-tk/GCV system can be monitored using bioluminescent imaging and tumor size measurement.Application of bioluminescence imaging to therapeutic intervention of herpes simplex virus type I – Thymidine kinase/ganciclovir in gliomaSu Jin Jang, Joo Hyun Kang, Kwang Il Kim, Tae Sup Lee, Yong Jin Lee, Kyo Chul Lee, Kwang Sun Woo, Wee Sup Chung, Hee Chung Kwon, Chun Jeih Ryu, Tae Hyun Choi, Chang Woon Choi, Sang Moo Lim, Gi Jeong Cheon10.1016/j.canlet.2010.04.028Cancer Letters 297, 1 (2010)2010-06-07Cancer Letters2010-06-072971S0304-3835(10)X0020-9Original Articles8490http://www.cancerletters.info/article/PIIS0304383510002533/abstract?rss=yesAbstract: Epigenetic modifications commonly associated with tumor development, such as histone deacetylation, may influence the resistance of some tumor cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) by regulating gene transcription of components of the TRAIL signalling pathway. In the present study we have analyzed the effect of six different histone deacetylase inhibitors (HDACi), belonging to the four classic structural families, on TRAIL-induced apoptosis in leukemic T cell lines. Non-toxic and functional doses of all HDACi but apicidin, similarly sensitized different leukemic T cell lines to TRAIL-induced apoptosis, while they showed no effect on the resistance of normal T lymphocytes. Sensitizing doses of vorinostat, valproic acid, sodium butyrate and MS-275 regulated the expression of TRAIL-R2, c-FLIP and Apaf-1 in leukemic cells while TSA modulated only the expression of Apaf-1. The synergistic effect of all HDACi and TRAIL was inhibited in Bcl-2-overexpressing leukemic T cells. Thus, different HDACi may affect the expression of different TRAIL-related genes, but regulation of the mitochondrial pathway seems to be essential for the TRAIL sensitizing effect of HDACi in leukemic T cells. Overall, HDACi represent a promising and safe strategy in combination with TRAIL for treatment of T-cell leukaemia.HDAC inhibitors with different gene regulation activities depend on the mitochondrial pathway for the sensitization of leukemic T cells to TRAIL-induced apoptosisJ.C. Morales, M.J. Ruiz-Magaña, D. Carranza, G. Ortiz-Ferrón, C. Ruiz-Ruiz10.1016/j.canlet.2010.04.029Cancer Letters 297, 1 (2010)2010-05-26Cancer Letters2010-05-262971S0304-3835(10)X0020-9Original Articles91100http://www.cancerletters.info/article/PIIS0304383510002545/abstract?rss=yesAbstract: Autophagy mediates cellular self-digestion to degrade cytoplasmic proteins and organelles and plays important roles in tumorigenesis. DJ-1 is an oncogene product in association with cancers and tumorigenesis. In this study, we show that knockdown of DJ-1 induces autophagy through activating JNK pathway to promote Beclin 1 transcription, whereas overexpression of DJ-1 inhibits these processes. Moreover, inhibition of JNK pathway by SP600125 blocks autophagy activation and p62 degradation induced by knockdown of DJ-1. Our findings suggest that DJ-1 regulates autophagy in a JNK-dependent manner. Thus, the involvement of DJ-1 in autophagy regulation may be involved in tumorigenesis.DJ-1, a cancer and Parkinson’s disease associated protein, regulates autophagy through JNK pathway in cancer cellsHaigang Ren, Kai Fu, Chenchen Mu, Bin Li, Dan Wang, Guanghui Wang10.1016/j.canlet.2010.05.001Cancer Letters 297, 1 (2010)2010-06-01Cancer Letters2010-06-012971S0304-3835(10)X0020-9Original Articles101108http://www.cancerletters.info/article/PIIS0304383510002569/abstract?rss=yesAbstract: The function of EZH2 in tumorigenesis and liver metastasis of pancreatic cancer has never been elucidated in vivo. EZH2 was overexpressed in pancreatic carcinomas and its overexpression was associated with tumor differentiation and pT status. Suppression of EZH2 caused a significant growth inhibition of pancreatic cancer cells in vitro and markedly diminished their tumorigenicity in vivo. Knock-down of EZH2 inhibited liver metastasis of pancreatic cancer in vivo. EZH2 has a crucial role in tumor growth and liver metastasis of pancreatic cancer.RNAi targeting EZH2 inhibits tumor growth and liver metastasis of pancreatic cancer in vivoYangchao Chen, Dan Xie, Wing Yin Li, Chi Man Cheung, Hong Yao, Ching Yu Chan, Chu-yan Chan, Fang-Ping Xu, Yan-Hui Liu, Joseph J.Y. Sung, Hsiang-fu Kung10.1016/j.canlet.2010.05.003Cancer Letters 297, 1 (2010)2010-05-31Cancer Letters2010-05-312971S0304-3835(10)X0020-9Original Articles109116http://www.cancerletters.info/article/PIIS0304383510002570/abstract?rss=yesAbstract: The purpose of this work is to study mechanisms underlying anti-tumor effects of farnesyltransferase inhibitors (FTIs) in non-small cell lung cancer (NSCLC). We demonstrate that mRNA and protein levels of Ras homologue enriched in brain (Rheb) are highly expressed both in NSCLC tissues and in NSCLC cell lines. Rheb expression levels correlate with phosphorylation of its downstream target S6 and the sensitivity of NSCLC cells to FTIs (R115777 and SCH66336)-induced growth inhibition and apoptosis. FTIs effectively and preferentially inhibited Rheb downstream signaling in NSCLC cells. Moreover, inhibition of Rheb functions by FTIs or dominant-negative Rheb mutants enhance the effects of cisplatin on NSCLC cells. Rheb-CSVL, a FTIs-resistant mutant, reduces the effects of FTIs on NSCLC cells. Our results suggest that Rheb is a critical target for FTIs therapy in NSCLC.Ras homologue enriched in brain is a critical target of farnesyltransferase inhibitors in non-small cell lung cancer cellsHang Zheng, Anling Liu, Bin Liu, Minghui Li, Hailang Yu, Xiaojun Luo10.1016/j.canlet.2010.05.004Cancer Letters 297, 1 (2010)2010-05-31Cancer Letters2010-05-312971S0304-3835(10)X0020-9Original Articles117125http://www.cancerletters.info/article/PIIS0304383510002582/abstract?rss=yesAbstract: γδ T cells can be an option for adoptive immunotherapy of cancer. The major obstacle to clinical application of γδ T cells is their low number and lack of a reliable method to expand them consistently and efficiently.We were able to expand γδ T cells with high purity in all donors regardless of their starting repertoire of γδ T cells. These ex vivo expanded γδ T cells are in early differentiation stage, can efficiently kill various tumors and inhibit growth of human lung cancer xenografts.This new approach for ex vivo expansion of human γδ T cells will open new horizons for clinical use of these cells.Adoptive immunotherapy of cancer using ex vivo expanded human γδ T cells: A new approachPouneh Dokouhaki, Mei Han, Betty Joe, Ming Li, Michael R. Johnston, Ming-Sound Tsao, Li Zhang10.1016/j.canlet.2010.05.005Cancer Letters 297, 1 (2010)2010-05-31Cancer Letters2010-05-312971S0304-3835(10)X0020-9Original Articles126136