C1B domain peptide of protein kinase Cγ significantly suppresses growth of human colon cancer cells in vitro and in an in vivo mouse xenograft model through induction of cell cycle arrest and apoptosis.

Abstract:

:Two peptides derived from the C1B domain of protein kinase Cγ (PKCγ) were shown to associate with classical PKC isozymes and modulate their activities. These C1B peptides are designated C1B1 (amino acid residues 101-112) and C1B5 (residues 141-151). Since PKC enzyme activity is shown to be involved in colon cancer development, the effect of C1B peptides on the growth of various human colon cancer cell lines was examined in vitro and in vivo. Sub-micromolar to micromolar levels of both C1B peptides induced approximately 60-70% growth attenuation in multiple colon cancer cell lines in a soft agar tumor colony assay; however, C1B5 peptide was not cytotoxic to normal colon epithelial cells in two dimensional culture. The effect of C1B5 peptide on colony growth of COLO205 cells was reversed by treatment with the PKCα/β inhibitor, Ro-32-0432. C1B peptide treatment attenuated COLO205 cells via two mechanisms: 1) cell cycle arrest and 2) stimulation of apoptosis. This is evident in G 2 arrest and increases in levels of cleaved caspase 3 and p53 phosphorylated at serine 20. Intratumoral injection of C1B5 peptide (20 mg/kg/day, every three days) markedly attenuated the growth of subcutaneous xenografts of COLO205 cells in SCID mice by 76% compared with the control. Taken together, these results strongly suggest that C1B peptides have negligible effects on normal tissues but are potentially effective chemotherapeutic agents for colon cancer.

journal_name

Cancer Biol Ther

journal_title

Cancer biology & therapy

authors

Kawabata A,Matsuzuka T,Doi C,Seiler G,Reischman J,Pickel L,Ayuzawa R,Nguyen TA,Tamura M

doi

10.4161/cbt.20840

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

880-9

issue

10

eissn

1538-4047

issn

1555-8576

pii

20840

journal_volume

13

pub_type

杂志文章
  • Furanodiene induces G2/M cell cycle arrest and apoptosis through MAPK signaling and mitochondria-caspase pathway in human hepatocellular carcinoma cells.

    abstract::Furanodiene (C15H20O), a pure compound isolated from Traditional Chinese medicine, Curcuma wenyujin, named Ezhu in Chinese, which structure was determined on the basis of NMR, MS and UV spectrum. In this study, we attempted to characterize in detail the signaling cascades resulted from furanodiene-induced apoptosis in...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.6.7.4317

    authors: Xiao Y,Yang FQ,Li SP,Gao JL,Hu G,Lao SC,Conceição EL,Fung KP,Wangl YT,Lee SM

    更新日期:2007-07-01 00:00:00

  • C7 peptide inhibits hepatocellular carcinoma metastasis by targeting the HGF/c-Met signaling pathway.

    abstract::Hepatocellular carcinoma (HCC), characterized by a high rate of metastasis and recurrence after surgery, is caused by malignant proliferation of hepatocytes with epigenetic and/or genetic mutations. In particular, abnormal activation of the hepatocyte growth factor (HGF)-/c-mesenchymal-epithelial transition receptor (...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2019.1647051

    authors: Zhao M,Wang Y,Liu Y,Zhang W,Liu Y,Yang X,Cao Y,Wang S

    更新日期:2019-01-01 00:00:00

  • No association between XRCC1 polymorphisms and survival in non-small-cell lung cancer patients treated with platinum-based chemotherapy.

    abstract:PURPOSE:genetic polymorphisms in DNA repair genes are thought to represent important determinants of platinum drug efficacy. The current study investigated whether single nucleotide polymorphisms (SNPs) in the X-ray repair cross complementing protein 1 (XRCC1) gene are associated with survival in non-small-cell lung ca...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.10.9.13238

    authors: Yuan P,Liu L,Wu C,Zhong R,Yu D,Wu J,Xu Y,Nie S,Miao X,Sun Y,Xu B,Lin D

    更新日期:2010-11-01 00:00:00

  • Cross-talk of WNT and FGF signaling pathways at GSK3beta to regulate beta-catenin and SNAIL signaling cascades.

    abstract::WNT and FGF signaling pathways cross-talk during a variety of cellular processes, such as human colorectal carcinogenesis, mouse mammary tumor virus (MMTV)-induced carcinogenesis, E2A-Pbx-induced leukemogenesis, early embryogenesis, body-axis formation, limb-bud formation, and neurogenesis. Canonical WNT signals are t...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.4161/cbt.5.9.3151

    authors: Katoh M,Katoh M

    更新日期:2006-09-01 00:00:00

  • ETS-TMPRSS2 fusion gene products in prostate cancer.

    abstract::Genes playing a role in carcinogenesis have often been identified through analysis of recurrent chromosomal rearrangements. Although such rearrangements are well known in leukemias, lymphomas, and sarcomas, they have not been well characterized in carcinomas. In the October 28, 2005 issue of Science, a study by Tomlin...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.5.3.2603

    authors: Ahlers CM,Figg WD

    更新日期:2006-03-01 00:00:00

  • EGFR signaling defines Mcl⁻1 survival dependency in neuroblastoma.

    abstract::The pediatric solid tumor neuroblastoma (NB) often depends on the anti-apoptotic protein, Mcl(-)1, for survival through Mcl(-)1 sequestration of pro-apoptotic Bim. High affinity Mcl(-)1 inhibitors currently do not exist such that novel methods to inhibit Mcl(-)1 clinically are in high demand. Receptor tyrosine kinases...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2014.1002333

    authors: Nalluri S,Peirce SK,Tanos R,Abdella HA,Karmali D,Hogarty MD,Goldsmith KC

    更新日期:2015-01-01 00:00:00

  • Acquired resistance of lung adenocarcinoma to EGFR-tyrosine kinase inhibitors gefitinib and erlotinib.

    abstract::Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, are the first targeted therapy drugs approved for the treatment of advanced non-small-cell lung cancer (NSCLC). Interestingly, treatment with these small molecule, reversible EGFR-TKIs leads to more positive respo...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.4161/cbt.9.8.11881

    authors: Xu Y,Liu H,Chen J,Zhou Q

    更新日期:2010-04-15 00:00:00

  • Post-biopsy rise in serum PSA. A potential tool for the dynamic evaluation of prostate cancer/prostatic intraepithelial neoplasia (PIN).

    abstract:OBJECTIVES:The biochemical response of prostatic cells to needle core biopsies is known to manifest as a rise in serum PSA. The aim of this study is to evaluate the PSA response to mechanical trauma in prostate cancer patients, when compared to benign controls. MATERIALS AND METHODS:50 consecutive patients undergoing ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.181

    authors: Bhanot S,Gopalakrishnan R,Oliver RT

    更新日期:2003-01-01 00:00:00

  • Paclitaxel-induced FasL-independent apoptosis and slow (non-apoptotic) cell death.

    abstract::Microtubule-active drugs, including paclitaxel (Taxol, PTX), cause mitotic arrest, and this can result in apoptosis. A recently study has reported that PTX mediates apoptosis by upregulating FasL in Jurkat and MDA-231 cells. In contrast to the previous report, we found that anti-FasL antibodies failed to inhibit PTX-i...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.53

    authors: Blagosklonny MV,Robey R,Sheikh MS,Fojo T

    更新日期:2002-03-01 00:00:00

  • Examining HSD3B1 as a possible biomarker to detect prostate cancer patients who are likely to progress on ADT.

    abstract::The Chemohormonal Therapy vs Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) was a randomized phase III trial that evaluated the outcomes of men with metastatic prostate cancer who received castration with or without docetaxel. Patients from this trial were genotyped in a recent ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2020.1796195

    authors: Handy WF,Schmidt KT,Price DK,Figg WD

    更新日期:2020-09-01 00:00:00

  • Copy-number variants in patients with a strong family history of pancreatic cancer.

    abstract::Copy-number variants such as germ-line deletions and amplifications are associated with inherited genetic disorders including familial cancer. The gene or genes responsible for the majority of familial clustering of pancreatic cancer have not been identified. We used representational oligonucleotide microarray analysi...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.6.10.4725

    authors: Lucito R,Suresh S,Walter K,Pandey A,Lakshmi B,Krasnitz A,Sebat J,Wigler M,Klein AP,Brune K,Palmisano E,Maitra A,Goggins M,Hruban RH

    更新日期:2007-10-01 00:00:00

  • Production of IL-1β by bone marrow-derived macrophages in response to chemotherapeutic drugs: synergistic effects of doxorubicin and vincristine.

    abstract::Cytotoxic chemotherapeutic drugs, especially when used in combination, are widely employed to treat a variety of cancers in patients but often lead to serious symptoms that negatively affect physical functioning and quality of life. There is compelling evidence that implicates cytotoxic chemotherapy-induced inflammati...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.29922

    authors: Wong J,Tran LT,Magun EA,Magun BE,Wood LJ

    更新日期:2014-10-01 00:00:00

  • Effects of Streptococcus thermophilus TH-4 on intestinal mucositis induced by the chemotherapeutic agent, 5-Fluorouracil (5-FU).

    abstract::Beneficial bacteria (probiotics) and probiotic-derived factors have the potential to ameliorate disorders of the intestine. The aim of this study was to compare live Streptococcus thermophilus TH-4 (TH-4), dead TH-4 and TH-4 supernatant in rats treated with 5-Fluorouracil. Rats were randomly allocated to five treatmen...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:

    authors: Whitford EJ,Cummins AG,Butler RN,Prisciandaro LD,Fauser JK,Yazbeck R,Lawrence A,Cheah KY,Wright TH,Lymn KA,Howarth GS

    更新日期:2009-03-15 00:00:00

  • Apoptotic response to 5-fluorouracil treatment is mediated by reduced polyamines, non-autocrine Fas ligand and induced tumor necrosis factor receptor 2.

    abstract::5-fluorouracil (5-FU) is the major chemotherapeutic agent for treatment of colorectal carcinoma, but the molecular mechanisms of response and resistance are not understood completely. We therefore studied the 5-FU dose response and time course of gene expression transcriptome changes in colon carcinoma cell lines that...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.2.5.532

    authors: Zhang W,Ramdas L,Shen W,Song SW,Hu L,Hamilton SR

    更新日期:2003-09-01 00:00:00

  • Hypoxia promotes chemotherapy resistance by down-regulating SKA1 gene expression in human osteosarcoma.

    abstract::Drug resistance has always been the main problem in osteosarcoma treatment, and hypoxia seems to be one of the many causes for drug resistance. Therefore, in this study, we investigated how hypoxia triggers chemotherapy resistance in osteosarcoma. We first screened hypoxia- and normoxia- cultured osteosarcoma cells in...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2017.1294285

    authors: Ma Q,Zhang Y,Liu T,Jiang K,Wen Y,Fan Q,Qiu X

    更新日期:2017-03-04 00:00:00

  • Remarkable enhancement of cytotoxicity of onconase and cepharanthine when used in combination on various tumor cell lines.

    abstract::Onconase (Onc), a ribonuclease from oocytes or early embryos of Northern Leopard frog (Rana pipiens), is cytostatic and cytotoxic to a variety of tumor lines in vitro, inhibits growth of tumors in animal in vivo models and is currently in Phase IIIb clinical trials for malignant mesothelioma where it displays antitumo...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.7.7.6172

    authors: Ita M,Halicka HD,Tanaka T,Kurose A,Ardelt B,Shogen K,Darzynkiewicz Z

    更新日期:2008-07-01 00:00:00

  • Vasculogenic mimicry is a marker of poor prognosis in prostate cancer.

    abstract::We investigated the role of vasculogenic mimicry (VM) in the progression of prostate cancer (PCa). Ninety-six patients who had undergone prostatectomy for treatment of PCa and for whom a complete record of clinical and follow-up data were available were reviewed. VM and matrix metalloproteinase-2 (MMP-2) were detected...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.19602

    authors: Liu R,Yang K,Meng C,Zhang Z,Xu Y

    更新日期:2012-05-01 00:00:00

  • Silencing of heparanase by siRNA inhibits tumor metastasis and angiogenesis of human breast cancer in vitro and in vivo.

    abstract::Expression of the heparanase gene is associated with invasive, angiogenic and metastatic potential of diverse malignant tumors and cell lines. Here we used RNA interference strategies to evaluate the role of human heparanase in breast malignancy and to explore the therapeutic potential of its specific targeting. The s...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.6.4.3888

    authors: Zhang ZH,Chen Y,Zhao HJ,Xie CY,Ding J,Hou YT

    更新日期:2007-04-01 00:00:00

  • Aurora A mediates cross-talk between N- and C-terminal post-translational modifications of p53.

    abstract::The serine/threonine protein kinase Aurora A is known to interact with and phosphorylate tumor suppressor p53 at Serine 215 (S215), inhibiting the transcriptional activity of p53. We show that Aurora A positively regulates human p53 protein levels and, using isogenic p53 wild-type and p53-null colorectal carcinoma cel...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.12.12.18141

    authors: Warnock LJ,Raines SA,Milner J

    更新日期:2011-12-15 00:00:00

  • A DNA repeat, NBL2, is hypermethylated in some cancers but hypomethylated in others.

    abstract::Hypermethylation at certain CpG-rich promoters and hypomethylation at repeated DNA sequences are very frequently found in cancers. We provide the first report that a DNA sequence (NBL2) can be either extensively hypermethylated or hypomethylated in cancer. Previously, it was shown that NBL2, a complex tandem DNA repea...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.4.4.1622

    authors: Nishiyama R,Qi L,Tsumagari K,Weissbecker K,Dubeau L,Champagne M,Sikka S,Nagai H,Ehrlich M

    更新日期:2005-04-01 00:00:00

  • Identification of miRNAs that are associated with tumor metastasis in neuroblastoma.

    abstract::The discovery of microRNAs (miRNAs) has opened a new avenue for both diagnosis and treatment of cancers. Accumulating experimental evidences indicate that miRNAs are aberrantly expressed in different tumor types and have a critical role in tumorigenesis. However, the miRNA expression profile in neuroblastoma (NB), one...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.9.6.10894

    authors: Guo J,Dong Q,Fang Z,Chen X,Lu H,Wang K,Yin Y,Cai X,Zhao N,Chen J,Zen K,Zhang J,Zhang CY

    更新日期:2010-03-15 00:00:00

  • Caveolin-1 is required for the upregulation of fatty acid synthase (FASN), a tumor promoter, during prostate cancer progression.

    abstract::Prostate cancer is the second leading cause of cancer-related deaths in men. Fatty acid synthase (FASN) is normally upregulated during human prostate cancer onset and metastatic progression and its expression positively correlates with the development of advanced metastatic disease. However, it remains unknown what mo...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.6.8.4447

    authors: Di Vizio D,Sotgia F,Williams TM,Hassan GS,Capozza F,Frank PG,Pestell RG,Loda M,Freeman MR,Lisanti MP

    更新日期:2007-08-01 00:00:00

  • Upregulation of the androgen receptor during prostate cancer progression.

    abstract::The androgen receptor is one of the central factors in mediating prostate cancer progression and is an important target for treatment. Several possible mechanisms have been put forth as to how it promotes this process. In the January 2004 issue of Nature Medicine, Chen et al. report that the androgen receptor is consi...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.3.3.785

    authors: Singh A,Figg WD

    更新日期:2004-03-01 00:00:00

  • Targeting of two aspects of metabolism in breast cancer treatment.

    abstract::Deregulated metabolism is gaining recognition as a hallmark of cancer cells, and is being explored for therapeutic potential. The Warburg effect is a metabolic phenotype that occurs in 90% of tumors, where glycolysis is favored despite the presence of oxygen. Dichloroacetate (DCA) is a pyruvate dehydrogenase kinase (P...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/15384047.2014.955992

    authors: Gang BP,Dilda PJ,Hogg PJ,Blackburn AC

    更新日期:2014-01-01 00:00:00

  • Analysis of chromosomes 9 and 11 aneuploidy frequency in pleural effusion of patients with and without malignancy: interphase FISH technique.

    abstract::Fluids of body cavities result in a series of pathophysiological events associated with non-malignant and malignant conditions that lead to the formation of exudative effusion. Diagnosis of effusion from the patients is frequently troublesome for the cytologist because of the differentiation and biological behavior of...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.4.2.1573

    authors: Cora T,Acar H,Ceran S,Bodur S

    更新日期:2005-02-01 00:00:00

  • Nucleophosmin/B23, a multifunctional protein that can regulate apoptosis.

    abstract::Nucleophosmin (NPM)/B23, a multifunctional nucleolar protein, is overexpressed in actively proliferating cells and cancer cells. B23 is a tumor marker and exerts its oncogenic effect through binding and suppressing numerous tumor suppressors. NPM-ALK, an aberrant fusion protein produced from t(2;5) translocation in an...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.4161/cbt.4.9.2072

    authors: Ye K

    更新日期:2005-09-01 00:00:00

  • Inactivation of miR-100 combined with arsenic treatment enhances the malignant transformation of BEAS-2B cells via stimulating epithelial -mesenchymal transition.

    abstract::Chronic arsenic treatment induces epithelial-mesenchymal transition (EMT) and promotes tumorigenicity, but the mechanism is unclear. MiR-100 has been shown to be involved in this biologic process. In this study, we hypothesize that inactivation of miR-100 combined with low concentration of arsenic exposure could promo...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2017.1345393

    authors: Yang J,Chen Z,Wang X,Xu M,Fang H,Li F,Liu Y,Jiang Y,Ding Y,Li J,Wang S

    更新日期:2017-12-02 00:00:00

  • Multiple tumor-suppressor genes on chromosome 3p contribute to head and neck squamous cell carcinoma tumorigenesis.

    abstract::Head and neck squamous cell carcinoma (HNSCC) remains a significant cause of morbidity and mortality. There has been a great interest in finding specific genomic changes which contribute to HNSCC tumorigenesis, especially within the chromosome 3p area, where high frequency of LOH (loss of heterozygosity) has been repo...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.10.7.12886

    authors: Lee DJ,Schönleben F,Banuchi VE,Qiu W,Close LG,Assaad AM,Su GH

    更新日期:2010-10-01 00:00:00

  • Small molecule inhibitors of IRES-mediated translation.

    abstract::Many genes controlling cell proliferation and survival (those most important to cancer biology) are now known to be regulated specifically at the translational (RNA to protein) level. The internal ribosome entry site (IRES) provides a mechanism by which the translational efficiency of an individual or group of mRNAs c...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2015.1071729

    authors: Vaklavas C,Meng Z,Choi H,Grizzle WE,Zinn KR,Blume SW

    更新日期:2015-01-01 00:00:00

  • The status of zinc in the development of hepatocellular cancer: an important, but neglected, clinically established relationship.

    abstract::Liver cancer (hepatocellular carcinoma, HCC) is increasing worldwide. About 75% of HCC cases result in death generally within one year. The factors responsible for the initiation and progression of HCC remain largely unknown and speculative, thereby impeding advancements in the development of effective therapeutic age...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.4161/cbt.27633

    authors: Costello LC,Franklin RB

    更新日期:2014-04-01 00:00:00