Effects of active bufadienolide compounds on human cancer cells and CD4+CD25+Foxp3+ regulatory T cells in mitogen-activated human peripheral blood mononuclear cells.

Abstract:

:The growth inhibitory effects of bufadienolide compounds were investigated in two intractable cancer cells, a human glioblastoma cell line U-87 and a pancreatic cancer cell line SW1990. Among four bufadienolide compounds, a dose-dependent cytotoxicity was observed in these cancer cells after treatment with gamabufotalin and arenobufagin. The IC50 values of the two compounds were 3-5 times higher in normal peripheral blood mononuclear cells (PBMCs) than these values for both cancer cell lines. However, similar phenomena were not observed for two other bufadienolide compounds, telocinobufagin and bufalin. These results thus suggest that gamabufotalin and arenobufagin possess selective cytotoxic activity against tumor cells rather than normal cells. Moreover, a clear dose-dependent lactate dehydrogenase (LDH) release, a well-known hallmark of necrosis, was observed in both cancer cells treated with gamabufotalin, suggesting that gamabufotalin-mediated cell death is predominantly associated with a necrosis-like phenotype. Of most importance, treatment with as little as 8 ng/ml of gamabufotalin, even an almost non-toxic concentration to PBMCs, efficiently downregulated the percentages of CD4+CD25+Foxp3+ regulator T (Treg) cells in mitogen-activated PBMCs. Given that Treg cells play a critical role in tumor immunotolerance by suppressing antitumor immunity, these results suggest that gamabufotalin may serve as a promising candidate, as an adjuvant therapeutic agent by manipulating Treg cells to enhance the efficacy of conventional anticancer drugs and lessen their side-effects. These findings provide insights into the clinical application of gamabufotalin for cancer patients with glioblastoma/pancreatic cancer based on its cytocidal effect against tumor cells as well as its depletion of Treg cells.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Yuan B,He J,Kisoh K,Hayashi H,Tanaka S,Si N,Zhao HY,Hirano T,Bian B,Takagi N

doi

10.3892/or.2016.4946

subject

Has Abstract

pub_date

2016-09-01 00:00:00

pages

1377-84

issue

3

eissn

1021-335X

issn

1791-2431

journal_volume

36

pub_type

杂志文章
  • microRNA-520a-3p inhibits proliferation and cancer stem cell phenotype by targeting HOXD8 in non-small cell lung cancer.

    abstract::Formation of cancer stem cells (CSCs) and increased cells proliferation are involved in tumorigenesis, tumour recurrence and therapy resistance and microRNA is essential for the development of the biological traits of CSCs and the increased cells proliferation. Studying molecular mechanism of tumorigenesis, tumour rec...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.5149

    authors: Liu Y,Miao L,Ni R,Zhang H,Li L,Wang X,Li X,Wang J

    更新日期:2016-12-01 00:00:00

  • Promoter methylation of the bone morphogenetic protein 6 gene in multiple myeloma.

    abstract::Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-β superfamily, are multifunctional signaling molecules that have become of increasing interest in cancer research. Recent observations suggest that alterations in BMPs and BMP signaling are associated...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2011.1548

    authors: Hashida Y,Nemoto Y,Imajoh M,Murakami M,Taniguchi A,Komatsu N,Yokoyama A,Daibata M

    更新日期:2012-03-01 00:00:00

  • Leucine zipper structure of TSC-22 (TGF-beta stimulated clone-22) markedly inhibits the anchorage-independent growth of salivary gland cancer cells.

    abstract::Several investigators have demonstrated that TGF-beta stimulated clone-22 (TSC-22) regulates cell growth and differentiation, and cell death. TSC-22 is a putative transcriptional regulator containing a leucine zipper-like structure and a nuclear export signal. We previously showed the cytoplasmic localization of TSC-2...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Hino S,Kawamata H,Omotehara F,Uchida D,Begum NM,Yoshida H,Sato M,Fujimori T

    更新日期:2002-03-01 00:00:00

  • Cannabinoids inhibit peptidoglycan-induced phosphorylation of NF-κB and cell growth in U87MG human malignant glioma cells.

    abstract::Nuclear factor (NF)-κB is the key transcription factor involved in the inflammatory responses, and its activation aggravates tumors. Peptidoglycan (PGN), a main cell wall component of Gram-positive bacteria, stimulates Toll-like receptor 2 (TLR-2) and activates a number of inflammat...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.1937

    authors: Echigo R,Sugimoto N,Yachie A,Ohno-Shosaku T

    更新日期:2012-10-01 00:00:00

  • The relationship between 5-fluorouracil sensitivity and single nucleotide polymorphisms of the orotate phosphoribosyl transferase gene in colorectal cancer.

    abstract::Orotate phosphoribosyl transferase (OPRT) is an enzyme playing an important role in exertion of the effect of 5-fluorouracil (5-FU). A type of gene polymorphism, single nucleotide polymorphism (SNP), is considered to be a factor affecting individual differences in exertion of drug effects, and its analysis has recentl...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Kitajima M,Takita N,Hata M,Maeda T,Sakamoto K,Kamano T,Ochiai T

    更新日期:2006-01-01 00:00:00

  • IL22 furthers malignant transformation of rat mesenchymal stem cells, possibly in association with IL22RA1/STAT3 signaling.

    abstract::Mesenchymal stem cells (MSCs) hold great promise as potential therapies for tumors through the delivery of various anticancer agents. However, exogenous tissue‑derived MSCs, such as those of bone marrow, have exhibited a tendency for malignant transformation in the tumor microenvironment. This issue remains controvers...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2019.7007

    authors: Cui X,Jing X,Yi Q,Xiang Z,Tian J,Tan B,Zhu J

    更新日期:2019-04-01 00:00:00

  • Advanced non-seminomatous germ cell cancer of the testis with brain metastases: feasibility of additional brain irradiation and whole body hyperthermia plus chemotherapy.

    abstract::Patients with brain metastases in disseminated non-seminomatous germ cell cancer of the testis are treated by combined modality, e.g., cisplatin-containing chemotherapy, whole brain irradiation and/or surgical excision. However, cure rates of patients refractory to that standard treatment are low (5-year survival rate...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.8.2.219

    authors: Feyerabend T,Wiedemann GJ,Steeves R

    更新日期:2001-03-01 00:00:00

  • Gastric-and-intestinal mixed endocrine cell phenotypic expression of carcinoid tumors in the rectum.

    abstract::We have previously demonstrated that gastric and intestinal endocrine cell (End-cell) marker expression is important for assessment of the histogenesis of endocrine cell tumors. However, the End-cell phenotypes of carcinoid tumors in the rectum remain largely unclear. We therefore examined marker expression of rectal ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Hirata Y,Mizoshita T,Mizushima T,Shimura T,Mori Y,Kubota E,Wada T,Ogasawara N,Tanida S,Kataoka H,Sasaki M,Kamiya T,Tsukamoto T,Tatematsu M,Joh T

    更新日期:2009-01-01 00:00:00

  • Methylation of CLDN6, FBN2, RBP1, RBP4, TFPI2, and TMEFF2 in esophageal squamous cell carcinoma.

    abstract::In the development and progression of cancer, tumor suppressor genes may be silenced by mechanisms such as methylation. Thus the discovery of new genes silenced by methylation may uncover new tumor suppressor genes, and improve our understanding of cancer biology. In this study we investigated the methylation of 19 ge...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or_00000325

    authors: Tsunoda S,Smith E,De Young NJ,Wang X,Tian ZQ,Liu JF,Jamieson GG,Drew PA

    更新日期:2009-04-01 00:00:00

  • Human umbilical vein endothelial cell vaccine suppresses the angiogenesis of esophageal squamous cell carcinoma in a humanized mouse model.

    abstract::The antitumor effect of the human umbilical vein endothelial cell (HUVEC) vaccine has been well documented; however, its anti‑angiogenic effects on human esophageal squamous cell carcinoma (ESCC) have yet to be studied. In the present study, a 'humanized' mouse model was established by transplanting NOD/SCID mice with...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6653

    authors: Liu H,Zhao J,Yang Y,Jin G,Zhang X,Wang D,Xie C,Liu K,Chen X,Li X,Tian F,Dong Z,Lu J

    更新日期:2018-11-01 00:00:00

  • Quercetin-induced autophagy flux enhances TRAIL-mediated tumor cell death.

    abstract::Quercetin is a potent cancer therapeutic agent and dietary antioxidant present in fruit and vegetables. Quercetin prevents tumor proliferation by inducing cell cycle arrest and is a well known cancer therapeutic agent and autophagy mediator. We investigated whether quercetin enhances TRAIL-induced tumor cell death and...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.3991

    authors: Moon JH,Eo SK,Lee JH,Park SY

    更新日期:2015-07-01 00:00:00

  • MicroRNA-1 functions as a potential tumor suppressor in osteosarcoma by targeting Med1 and Med31.

    abstract::MicroRNA-1 (miR-1) has been shown to function as a critical gene regulator in multiple types of cancers. However, the role of miR-1 in osteosarcoma has not been totally clarified. In the present study, we investigated the effects of miR-1 on osteosarcoma and the underlying mechanism. We found that miR-1 was downregula...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3274

    authors: Jiang C,Chen H,Shao L,Wang Q

    更新日期:2014-09-01 00:00:00

  • Differential expression of neuropilin-1 in malignant and benign prostatic stromal tissue.

    abstract::Neuropilin-1 (NRP-1), a co-receptor for VEGF165, is overexpressed in various prostate cancer cell lines and in advanced prostate tumors. However, distribution of the NRP-1 in prostate tumors has not yet been evaluated. Using immunohistochemical analysis, we evaluated 21 archival prostate tumors and 5 benign glands for...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Vanveldhuizen PJ,Zulfiqar M,Banerjee S,Cherian R,Saxena NK,Rabe A,Thrasher JB,Banerjee SK

    更新日期:2003-09-01 00:00:00

  • sATP‑binding cassette subfamily G member 2 enhances the multidrug resistance properties of human nasal natural killer/T cell lymphoma side population cells.

    abstract::Extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKL) is a rare type of non‑Hodgkin's lymphoma that is associated with limited effective treatment options and unfavorable survival rate, which is partly the result of multidrug resistance (MDR). The presence of side population (SP) cells‑SNK‑6/ADM‑SP (SSP) c...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2020.7722

    authors: Wu S,Zhang X,Dong M,Yang Z,Zhang M,Chen Q

    更新日期:2020-10-01 00:00:00

  • Serenoa repens induces growth arrest and apoptosis of human multiple myeloma cells via inactivation of STAT 3 signaling.

    abstract::Serenoa repens, a palm species native to the Southeastern United States, is one of the widely used phytotherapeutic agents in benign prostatic hyperplasia. In this study, we found for the first time that Serenoa repens induced growth arrest of a variety of human leukemia cells including U266 and RPMI 8226 multiple mye...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Che Y,Hou S,Kang Z,Lin Q

    更新日期:2009-08-01 00:00:00

  • Actin disruption agents induce phosphorylation of histone H2AX in human breast adenocarcinoma MCF-7 cells.

    abstract::Modified actin dynamics are a unique feature of transformed cancer cells and thereby promising targets for cancer chemotherapy. While latrunculin B (LB) and pectenotoxin-2 (PTX-2), both derived from natural sources, inhibit actin polymerization, jasplakinolide (JSP) prevents actin depolymerization. The purpose of this...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2011.1214

    authors: Shin IJ,Ahn YT,Kim Y,Kim JM,An WG

    更新日期:2011-05-01 00:00:00

  • Loss of heterozygosity of nucleotide excision repair factors in sporadic oral squamous cell carcinoma using microdissected tissue.

    abstract::The deficiencies of nucleotide excision repair (NER) factors are involved in rare genetic diseases such as xeroderma pigmentosum (XP) with increased risk of developing cancer on sun-exposed areas of the skin. However, the abnormality of NER factors in human sporadic carcinoma remains unclear. Loss of heterozygosity (L...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.8.5.1133

    authors: Miyashita H,Mori S,Tanda N,Nakayama K,Kanzaki A,Sato A,Morikawa H,Motegi K,Takebayashi Y,Fukumoto M

    更新日期:2001-09-01 00:00:00

  • miR-375 inhibits the invasion and metastasis of colorectal cancer via targeting SP1 and regulating EMT-associated genes.

    abstract::Accumulating evidence has shown that aberrantly expressed microRNAs (miRNAs) are associated with tumor development and progression. Our previous study found that microRNA-375 (miR-375) was downregulated in colorectal cancer (CRC), but little is known concerning the role of miR-375 and the related mechanism in CRC deve...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4834

    authors: Cui F,Wang S,Lao I,Zhou C,Kong H,Bayaxi N,Li J,Chen Q,Zhu T,Zhu H

    更新日期:2016-07-01 00:00:00

  • Preferentially enhanced gene expression from a synthetic human telomerase reverse transcriptase promoter in human cancer cells.

    abstract::Although the human telomerase reverse transcriptase (hTERT) promoter can regulate cancer-specific genes, it is generally too weak to be effective. We therefore attempted to improve the potency of synthetic hTERT promoters by fusing the core element (E) of the hTERT promoter (H) and the tripartite leader sequence (T) f...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Kim SJ,Lee HS,Shin JH,Kim CG,Jeong S,Park K,Choe H,Lee H

    更新日期:2006-11-01 00:00:00

  • SPARC expression is negatively correlated with clinicopathological factors of gastric cancer and inhibits malignancy of gastric cancer cells.

    abstract::Secreted protein acidic and rich in cysteine (SPARC) is a glycoprotein which plays multiple roles in different types of cancer. Our previous study showed that SPARC overexpression inhibited the growth and angiogenesis of tumors, and reduced expression of vascular endothelial growth factor (VEGF). However, the relation...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3118

    authors: Zhang J,Wang P,Zhu J,Wang W,Yin J,Zhang C,Chen Z,Sun L,Wan Y,Wang X,Chen G,Liu Y

    更新日期:2014-05-01 00:00:00

  • Identification and characterization of cancer stem-like cells from primary carcinoma of the cervix uteri.

    abstract::Like many other solid tumors, cervical cancer contains a heterogeneous population of cancer cells. Several investigators have identified putative stem cells from solid tumors and cancer cell lines via the capacity to self renew and drive tumor formation. The aim of this study was to identify and characterize a cancer ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or_00000545

    authors: Feng D,Peng C,Li C,Zhou Y,Li M,Ling B,Wei H,Tian Z

    更新日期:2009-11-01 00:00:00

  • GnRH agonists and antagonists decrease the metastatic progression of human prostate cancer cell lines by inhibiting the plasminogen activator system.

    abstract::Prostate cancer (PCa) growth initially depends on circulating androgens. Gonadotropin-releasing hormone (GnRH) agonists are currently used for the treatment of PCa. However, after an initial responsiveness to hormonal deprivation, PCa progresses and metastasizes. Recently, also GnRH antagonists have been used for clin...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.15.2.393

    authors: Dondi D,Festuccia C,Piccolella M,Bologna M,Motta M

    更新日期:2006-02-01 00:00:00

  • Activation of NLRP3 inflammasome promotes the proliferation and migration of esophageal squamous cell carcinoma.

    abstract::Inflammasomes can identify endogenous danger signals as an inflammatory immune response. As the most common inflammasome, the NLR pyrin family domain containing 3 (NLRP3) inflammasome is associated with the pathogenesis of different tumors. However, the function of the NLRP3 inflammasome in esophageal cancer (EC) has ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2020.7493

    authors: Yu S,Yin JJ,Miao JX,Li SG,Huang CZ,Huang N,Fan TL,Li XN,Wang YH,Han SN,Zhang LR

    更新日期:2020-04-01 00:00:00

  • Comparison of 18F-fluoro-2-deoxyglucose positron emission tomography and gallium-67 citrate scintigraphy for detecting malignant lymphoma.

    abstract::This study evaluates and compares the accuracy of positron emission tomography with 18F-fluoro-2-deoxyglucose (FDG-PET) and gallium-67 citrate (Ga-67) scintigraphy in identifying disease sites in patients with malignant lymphoma at initial diagnosis or relapse. Histology subgroups included low (n=5), intermediate (n=6...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Shen YY,Kao A,Yen RF

    更新日期:2002-03-01 00:00:00

  • Avemar, a nontoxic fermented wheat germ extract, attenuates the growth of sensitive and 5-FdUrd/Ara-C cross-resistant H9 human lymphoma cells through induction of apoptosis.

    abstract::Avemar (MSC) is a nontoxic fermented wheat germ extract, which has been shown to significantly improve the survival rate in patients suffering from various malignancies. We investigated its effects in sensitive and 5-FdUrd/Ara-C cross-resistant H9 human lymphoma cells. After 48 and 72 h of incubation, Avemar inhibited...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Saiko P,Ozsvar-Kozma M,Graser G,Lackner A,Grusch M,Madlener S,Krupitza G,Jaeger W,Hidvegi M,Agarwal RP,Fritzer-Szekeres M,Szekeres T

    更新日期:2009-03-01 00:00:00

  • Silencing of argininosuccinate lyase inhibits colorectal cancer formation.

    abstract::Arginine and nitric oxide (NO) are important mediators of tumorigenesis in various types of cancer. Dysregulation of NO content by argininosuccinate lyase (ASL) has been previously demonstrated to inhibit the proliferation of liver and breast cancer cells. However, the function of ASL in colon cancer is not well defin...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.5221

    authors: Huang HL,Chen WC,Hsu HP,Cho CY,Hung YH,Wang CY,Lai MD

    更新日期:2017-01-01 00:00:00

  • Efficacy of oral UFT plus leucovorin therapy for colon cancer with ovarian and multiple liver metastases: report of two cases.

    abstract::Case 1: a patient was diagnosed as having ascending colon cancer with right ovarian metastasis, and underwent palliative right hemicolectomy plus oophorectomy. The tumor was a well-differentiated adenocarcinoma with right ovarian metastasis, and the disease was classified as stage IV. Oral chemotherapy with UFT plus L...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.8.5.1079

    authors: mukai M,Moriya H,Himeno S,Oida Y,mukohyama S,Nishi T,Nakasaki H,Satoh S,Makuuchi H

    更新日期:2001-09-01 00:00:00

  • The Das-1 immunostain is useful for discriminating metastatic colon adenocarcinoma from cholangiocarcinoma and hepatocellular carcinoma.

    abstract::The distinction between cholangiocarcinoma, hepatocellular carcinoma and liver metastasis is important but at times difficult solely on microscopic appearances. The Das-1 immunostain exhibits specificity for colonic epithelium. However, its staining of cholangiocarcinomas and hepatocellular carcinomas has not been ext...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Zimmerman RL,Das KM,Fogt F,Burke M,Murakata LA

    更新日期:2002-11-01 00:00:00

  • Differential expression profiling of gene response to ionizing radiation in two endometrial cancer cell lines with distinct radiosensitivities.

    abstract::Although radiotherapy is routinely administered to high-risk endometrial carcinoma and offer a significant disease-free survival advantage, the therapeutic effect is sometimes limited by the occurrence of radioresistance. To determine the patterns of gene expression responsible for the radioresistance and to search fo...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Du XL,Jiang T,Wen ZQ,Li QS,Gao R,Wang F

    更新日期:2009-03-01 00:00:00

  • Frequent CYP1A1 expression in gastric cancers and their related lesions.

    abstract::CYP1A1 expression in various tissues of 43 gastric cancer cases was analyzed with frozen tissue array-based immunohistochemical staining (IHC), RT-PCR, Western blot analysis and EROD (7-ethoxyresourfin-O-deethylase) assay. CYP1A1 was detected immunohistochemically in 86% (37/43) of gastric cancers, in both 57% (4/7) o...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Zhang KL,Ma JX,Chen XY,Sun Y,Kong QY,Liu J,Li H

    更新日期:2004-12-01 00:00:00