23 results match your criteria rottlerin-induced apoptosis

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Rottlerin inhibits cell growth and invasion via down-regulation of EZH2 in prostate cancer.

Cell Cycle 2018 15;17(21-22):2460-2473. Epub 2018 Nov 15.

a The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Soochow University , Suzhou , China.

Rottlerin as a natural agent, which is isolated from Mallotus philippinensis, has been identified to play a critical role in tumor inhibition. However, the molecular mechanism of rottlerin-mediated anti-tumor activity is still ambiguous. It has been reported that EZH2 exhibits oncogenic functions in a variety of human cancers. Read More

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November 2019

Rottlerin upregulates DDX3 expression in hepatocellular carcinoma.

Biochem Biophys Res Commun 2018 01 2;495(1):1503-1509. Epub 2017 Dec 2.

Department of General Surgery, The First People's Hospital of Wu Jiang, Suzhou, Jiangsu, 215200, China. Electronic address:

Rottlerin has been reported to exert its anti-tumor activity in various types of human cancers. However, the underlying molecular mechanism has not been fully elucidated. In the current study, we explored whether rottlerin exhibits its tumor suppressive function in hepatocellular carcinoma cells. Read More

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January 2018

Inhibition of Notch-1 pathway is involved in rottlerin-induced tumor suppressive function in nasopharyngeal carcinoma cells.

Oncotarget 2017 Sep 8;8(37):62120-62130. Epub 2017 Jul 8.

The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.

Recent studies have revealed that rottlerin is a natural chemical drug to exert its anti-cancer activity. However, the molecular mechanisms of rottlerin-induced tumor suppressive function have not been fully elucidated. Notch signaling pathway has been characterized to play a crucial role in tumorigenesis. Read More

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September 2017

Rottlerin as a novel chemotherapy agent for adrenocortical carcinoma.

Oncotarget 2017 Apr;8(14):22825-22834

Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong, P.R. China.

Adrenocortical carcinoma (ACC) is a rare, but aggressive endocrine malignancy with a generally poor clinical outcome. There is no effective therapy for advanced and metastatic ACC. In our study, we found that an existing drug (rottlerin) exerted its tumour-suppressive function in ACC. Read More

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Rottlerin-induced autophagy leads to apoptosis in bladder cancer cells.

Oncol Lett 2016 Dec 13;12(6):4577-4583. Epub 2016 Oct 13.

Institute of Urology, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China; Key Laboratory of Urological Diseases in Gansu Province, Lanzhou University, Lanzhou, Gansu 730030, P.R. China.

It has been well-established that apoptosis contributes to cancer cell death; however, the role of autophagy in cancer cell death remains unclear. The aim of the present study was to investigate the effects of rottlerin, a traditional Indian medicine, on cell growth inhibition and autophagy in EJ human bladder carcinoma cells . Cell viability, measured by MTT assay, was found to be suppressed in a dose- and time-dependent manner. Read More

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December 2016

Rottlerin inhibits cell growth and invasion via down-regulation of Cdc20 in glioma cells.

Oncotarget 2016 Oct;7(43):69770-69782

The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou, China.

Rottlerin, isolated from a medicinal plant Mallotus phillippinensis, has been demonstrated to inhibit cellular growth and induce cytoxicity in glioblastoma cell lines through inhibition of calmodulin-dependent protein kinase III. Emerging evidence suggests that rottlerin exerts its antitumor activity as a protein kinase C inhibitor. Although further studies revealed that rottlerin regulated multiple signaling pathways to suppress tumor cell growth, the exact molecular insight on rottlerin-mediated tumor inhibition is not fully elucidated. Read More

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October 2016

Rottlerin exerts its anti-tumor activity through inhibition of Skp2 in breast cancer cells.

Oncotarget 2016 Oct;7(41):66512-66524

The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.

Studies have investigated the tumor suppressive role of rottlerin in carcinogenesis. However, the molecular mechanisms of rottlerin-induced anti-tumor activity are largely unclear. Skp2 (S-phase kinase associated protein 2) has been validated to play an oncogenic role in a variety of human malignancies. Read More

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October 2016

The Unfolded Protein Response Plays a Predominant Homeostatic Role in Response to Mitochondrial Stress in Pancreatic Stellate Cells.

PLoS One 2016 5;11(2):e0148999. Epub 2016 Feb 5.

Pancreatic Research Group, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.

Activated pancreatic stellate cells (PaSC) are key participants in the stroma of pancreatic cancer, secreting extracellular matrix proteins and inflammatory mediators. Tumors are poorly vascularized, creating metabolic stress conditions in cancer and stromal cells that necessitate adaptive homeostatic cellular programs. Activation of autophagy and the endoplasmic reticulum unfolded protein response (UPR) have been described in hepatic stellate cells, but the role of these processes in PaSC responses to metabolic stress is unknown. Read More

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Activation of PKC-δ in HTLV-1-infected T cells.

Int J Oncol 2015 Apr 26;46(4):1609-18. Epub 2015 Jan 26.

Department of Pathology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852‑8523, Japan.

Protein kinase C (PKC)-δ is a member of the PKC family. It has been implicated in tumor suppression as well as survival of various cancers. The aggressive malignancy of T lymphocytes known as adult T-cell leukemia (ATL) is associated with human T-cell leukemia virus type 1 (HTLV-1) infection. Read More

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Rottlerin-induced autophagy leads to the apoptosis in breast cancer stem cells: molecular mechanisms.

Mol Cancer 2013 Dec 23;12(1):171. Epub 2013 Dec 23.

Department of Pharmacology, Toxicology and Therapeutics, and Internal Medicine, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.

Background: Autophagy is an indispensable lysosomal self-digestion process involved in the degradation of aggregated proteins and damaged organelles. Autophagy is associated with the several pathological processes, including cancer. Cancer stem cells (CSCs) play significant roles in cancer initiation, progression and drug resistance. Read More

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December 2013

Alternative Pathways of Cancer Cell Death by Rottlerin: Apoptosis versus Autophagy.

Evid Based Complement Alternat Med 2012 20;2012:980658. Epub 2012 Dec 20.

Department of Physiology, University of Siena, Via Aldo Moro, 7-53100 Siena, Italy.

Since the ability of cancer cells to evade apoptosis often limits the efficacy of radiotherapy and chemotherapy, autophagy is emerging as an alternative target to promote cell death. Therefore, we wondered whether Rottlerin, a natural polyphenolic compound with antiproliferative effects in several cell types, can induce cell death in MCF-7 breast cancer cells. The MCF-7 cell line is a good model of chemo/radio resistance, being both apoptosis and autophagy resistant, due to deletion of caspase 3 gene, high expression of the antiapoptotic protein Bcl-2, and low expression of the autophagic Beclin-1 protein. Read More

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January 2013

Rottlerin potentiates camptothecin-induced cytotoxicity in human hormone refractory prostate cancers through increased formation and stabilization of topoisomerase I-DNA cleavage complexes in a PKCδ-independent pathway.

Biochem Pharmacol 2012 Jul 2;84(1):59-67. Epub 2012 Apr 2.

School of Pharmacy, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan.

Combination therapy, which can optimize killing activity to cancers and minimize drug resistance, is a mainstream therapy against hormone-refractory prostate cancers (HRPCs). Rottlerin, a natural polyphenolic component, synergistically increased PC-3 (a HRPC cell line) apoptosis induced by camptothecin (a topoisomerase I inhibitor). Using siRNA technique to knockdown protein kinase C-δ (PKCδ), the data showed that rottlerin-mediated synergistic effect was PKCδ-independent, although rottlerin has been used as a PKCδ inhibitor. Read More

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Rottlerin induces apoptosis of HT29 colon carcinoma cells through NAG-1 upregulation via an ERK and p38 MAPK-dependent and PKC δ-independent mechanism.

Chem Biol Interact 2012 Apr 5;197(1):1-7. Epub 2012 Mar 5.

Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu, Republic of Korea.

Rottlerin, a selective inhibitor of novel isoforms of protein kinase C δ (PKC δ), has been shown to exert multiple effects on cancer cells, including inhibition of cell proliferation and migration. However, the molecular mechanisms responsible for these effects are not fully understood. We found that rottlerin dramatically induced non-steroidal anti-inflammatory drug activated gene-1 (NAG-1) expression in both p53 wild-type and p53-null cancer cell lines, suggesting that NAG-1 upregulation is a common response to rottlerin that occurs independently of p53 in multiple cell lines. Read More

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Rottlerin induces apoptosis via death receptor 5 (DR5) upregulation through CHOP-dependent and PKC delta-independent mechanism in human malignant tumor cells.

Carcinogenesis 2009 May 26;30(5):729-36. Epub 2008 Nov 26.

Department of Immunology and Chronic Disease Research Center and Institute for Medical Science, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu 700-712, South Korea.

Rottlerin has been shown to induce antiproliferation and apoptosis of human cancer cell lines. In this study, we demonstrate a novel mechanism of rottlerin-induced apoptosis via death receptor (DR) 5 upregulation. We found that treatment with rottlerin significantly induces DR5 expression both at its messenger RNA and protein levels. Read More

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Rottlerin induces pro-apoptotic endoplasmic reticulum stress through the protein kinase C-delta-independent pathway in human colon cancer cells.

Apoptosis 2008 Nov;13(11):1378-85

Department of Immunology, Chronic Disease Research Center, Institute for Medical Science, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu 700-712, South Korea.

Rottlerin, a compound reported to be a PKC delta-selective inhibitor, has been shown to induce growth arrest or apoptosis of human cancer cell lines. In our study, rottlerin dose-dependently induced apoptotic cell death in colon carcinoma cells. Treatment of HT29 human colon carcinoma cells with rottlerin was found to induce a number of signature ER stress markers; phosphorylation of eukaryotic initiation factor-2alpha (eIF-2alpha), ER stress-specific XBP1 splicing, and up-regulation of glucose-regulated protein (GRP)-78 and CCAAT/enhancer-binding protein-homologous protein (CHOP). Read More

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November 2008

Rottlerin induces autophagy and apoptotic cell death through a PKC-delta-independent pathway in HT1080 human fibrosarcoma cells: the protective role of autophagy in apoptosis.

Autophagy 2008 Jul 7;4(5):650-8. Epub 2008 Apr 7.

Department of Biochemistry, Chungnam National University, Munhwa-dong, Joong-gu, Daejeon, Korea.

Rottlerin is widely used as a protein kinase C-delta inhibitor. Recently, several reports have shown the possible apoptosis-inducing effect of rottlerin in some cancer cell lines. Here we report that rottlerin induces not only apoptosis but also autophagy via a PKC-delta-independent pathway in HT1080 human fibrosarcoma cells. Read More

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Down-regulation of caspase-2 by rottlerin via protein kinase C-delta-independent pathway.

Cancer Res 2008 Apr;68(8):2795-802

Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.

Protein kinase C-delta (PKC delta) plays an important role in DNA damage-induced apoptosis. We have previously shown that the PKC delta inhibitor rottlerin protects against cisplatin-induced apoptosis acting upstream of caspase-9. In the present study, we have investigated if rottlerin regulates caspase-2 activation. Read More

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Tissue transglutaminase inhibits autophagy in pancreatic cancer cells.

Mol Cancer Res 2007 Mar;5(3):241-9

Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

Elevated expression of tissue transglutaminase (TG2) in cancer cells has been implicated in the development of drug resistance and metastatic phenotypes. However, the role and the mechanisms that regulate TG2 expression remain elusive. Here, we provide evidence that protein kinase Cdelta (PKCdelta) regulates TG2 expression, which in turn inhibits autophagy, a type II programmed cell death, in pancreatic cancer cells that are frequently insensitive to standard chemotherapeutic agents. Read More

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Mechanisms of apoptosis-induction by rottlerin: therapeutic implications for B-CLL.

Leukemia 2006 Mar;20(3):514-20

3rd Department of Medicine, Technical University of Munich, Munich, Germany.

Constitutively activated signaling pathways contribute to the apoptosis-defect of B-CLL cells. Protein kinase C-delta is a permanently activated kinase and a putative downstream target of phosphatidylinositol-3 kinase in B-CLL. Blockade of protein kinase C-delta (PKC-delta) by the highly specific inhibitor rottlerin induces apoptosis in chronic lymphocytic leukaemia (CLL) cells. Read More

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Rottlerin sensitizes glioma cells to TRAIL-induced apoptosis by inhibition of Cdc2 and the subsequent downregulation of survivin and XIAP.

Oncogene 2005 Jan;24(5):838-49

Institute for Medical Sciences, Ajou University School of Medicine, Suwon 442-749, South Korea.

In the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant glioma cells, treatment with TRAIL in combination with subtoxic doses of rottlerin induced rapid apoptosis. While the proteolytic processing of procaspase-3 by TRAIL was partially blocked in these cells, treatment with rottlerin efficiently recovered TRAIL-induced activation of caspases. Treatment with rottlerin significantly decreased Cdc2 activity through the downregulation of cyclin A, cyclin B, and Cdc2 proteins, whereas the sensitizing effect of rottlerin on TRAIL-induced apoptosis was independent of PKCdelta activity. Read More

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January 2005

Protein kinase C delta is not activated by caspase-3 and its inhibition is sufficient to induce apoptosis in the colon cancer line, COLO 205.

Cell Signal 2005 Feb;17(2):253-62

Division of Medical Sciences, The Medical School, University of Birmingham, B15 2TT, UK.

Activation of protein kinase C delta (PKCdelta) is believed to be pro-apoptotic. PKCdelta is reported to be reduced in colon cancers. Using a colon cancer cell line, COLO 205, we have examined the roles of PKCdelta in apoptosis and of caspase-3 in the activation and inhibition of PKCdelta. Read More

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February 2005

Anti-apoptotic effect of atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, on cardiac myocytes through protein kinase C activation.

Clin Exp Pharmacol Physiol 2004 May-Jun;31(5-6):360-4

The 4th Department of Internal Medicine, Shimane Medical University, Shimane, Japan.

Pleiotropic effects of statins, which are independent of lipid lowering, have been reported. In the present study, we examined the effect of a statin on apoptosis of adult rat cultured cardiac myocytes. We used the protein kinase C (PKC) inhibitors staurosporine (1 micro mol/L), chelerythrine (10 micro mol/L) and rottlerin (5 micro mol/L) to induce myocyte apoptosis. Read More

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January 2005

Rottlerin sensitizes colon carcinoma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis via uncoupling of the mitochondria independent of protein kinase C.

Cancer Res 2003 Aug;63(16):5118-25

Division of Molecular Therapeutics, Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

Signaling pathways involved in survival responses may attenuate the apoptotic response to the cytotoxic tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in human colon carcinomas. In six lines examined, three were sensitive (GC(3)/c1, VRC(5)/c1, HCT116), HT29 demonstrated intermediate sensitivity, and RKO and HCT8 were resistant to TRAIL-induced apoptosis. Calphostin c [an inhibitor of classic and novel isoforms of protein kinase C (PKC)] sensitized five of six cell lines to TRAIL, whereas Go6976, (inhibitor of classic PKC isoforms), did not influence TRAIL sensitivity. Read More

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