Influence of pH on the cytotoxicity of cisplatin in EMT6 mouse mammary tumor cells.

Abstract:

:Pathophysiological factors exist within solid tumors that lead to a low pH environment. Therefore, pH-sensitive cancer chemotherapeutic agents may selectively target and kill tumor cells while sparing the normal tissue from toxicity. Using colony forming assays to assess cell survival, we found that EMT6 mouse mammary tumor cells were more sensitive to cisplatin cytotoxicity when cultured in pH 6.0 medium than in pH 7.2, 6.8, or 6.4 medium. The pH-dependent cytotoxicity of cisplatin resulted from an increase in cisplatin accumulation and an increase in the amount of DNA cross-links at pH 6.0 compared with pH 7.2. Because DNA is the cytotoxic target of cisplatin, intracellular pH (pHi) may be an important factor in determining the cytotoxicity of anticancer drugs at low extracellular pH (pHe). Therefore, manipulating the pHi of cells could be one method to enhance the effectiveness of the pH-sensitive chemotherapeutic agents. The pHi of EMT6 cells varied with pHe: at pHe 7.2, pHi was 7.54; at pHe 6.8, pHi was 7.29; at pHe 6.4, pHi was 7.02; and at pHe 6.0, pHi was 6.64. Using inhibitors to the ion transport mechanisms which regulate pHi, 5-N,N-hexamethylene amiloride (NHMA) and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), the pHi and pHe of EMT6 cells were equilibrated. To evaluate the importance of pHi in determining drug toxicity, cell survival was determined for cells treated with cisplatin in the presence of NHMA and SITS. Cells cultured with NHMA and SITS were less sensitive to cisplatin. The cisplatin resistance obtained was independent of pH and could be attributed to the presence of SITS.

journal_name

Oncol Res

journal_title

Oncology research

authors

Laurencot CM,Kennedy KA

subject

Has Abstract

pub_date

1995-01-01 00:00:00

pages

371-9

issue

7-8

eissn

0965-0407

issn

1555-3906

journal_volume

7

pub_type

杂志文章
  • Synthesis and biological evaluation of novel bis-aziridinylnaphthoquinone derivatives.

    abstract::A series of bis-aziridinylnaphthoquinone derivatives has been prepared. The cytotoxic activities and DNA alkylation abilities of these synthetic bis-aziridinylnaphthoquinone derivatives were investigated. They displayed significant cytotoxicity against human carcinomna cell lines and weak cytotoxic activities against ...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:

    authors: Huang ST,Kuo HS,Lin CM,Tsai HD,Peng YC,Chen CT,Lin YL

    更新日期:2003-01-01 00:00:00

  • TNF-alpha induction of A1 expression in human cancer cells.

    abstract::A1, a member of the Bcl-2 gene family, was originally identified as a hemopoietic-specific early response gene. Later it was found that A1 was overexpressed in human stomach cancer tissues and was induced by tumor necrosis factor-alpha (TNF-alpha) in human vascular endothelial cells. However, its expression in human c...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:

    authors: Pang XP,Hershman JM,Karsan A

    更新日期:1997-01-01 00:00:00

  • miR-641 Functions as a Tumor Suppressor by Targeting MDM2 in Human Lung Cancer.

    abstract::Lung cancer is the leading cause of deaths due to cancer. Studies suggest an important role of microRNAs (miRNAs) in a variety of cancers, including lung cancer. In the present study, we evaluated the role of miR-641 in human lung cancer A549 cells. Quantitative RT-PCR and Western blot were used to measure mRNA and pr...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:10.3727/096504017X15021536183490

    authors: Kong Q,Shu N,Li J,Xu N

    更新日期:2018-06-11 00:00:00

  • Crude Flavonoid Extract of Medicinal Herb Zingibar officinale Inhibits Proliferation and Induces Apoptosis in Hepatocellular Carcinoma Cells.

    abstract::There is an urgent need to improve the clinical management of hepatocellular carcinoma (HCC), one of the most common causes of global cancer-related deaths. Zingibar officinale is a medicinal herb used throughout history for both culinary and medicinal purposes. It has antioxidant, anticarcinogenic, and free radical s...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:10.3727/096504016X14816352324532

    authors: Elkady AI,Abu-Zinadah OA,Hussein RAEH

    更新日期:2017-07-05 00:00:00

  • Structure-activity relationship of 9-methylstreptimidone, a compound that induces apoptosis selectively in adult T-cell leukemia cells.

    abstract::We previously reported that 9-methylstreptimidone, a piperidine compound isolated from a culture filtrate of Streptomyces, induces apoptosis selectively in adult T-cell leukemia cells. It was screened for a compound that inhibits LPS-induced NF-kappaB and NO production in mouse macrophages. However, 9-methystreptimido...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:10.3727/096504012x13425470196056

    authors: Takeiri M,Ota E,Nishiyama S,Kiyota H,Umezawa K

    更新日期:2012-01-01 00:00:00

  • Potential Role of CD133 Expression in the Susceptibility of Human Liver Cancer Stem-Like Cells to TRAIL.

    abstract::Hepatocellular carcinoma (HCC) is one of the most common malignancies, with a poor prognosis and high recurrence rate. In the present study, we identified CD133, one of the markers of cancer stem cells, as a novel molecular target of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In four human HCC ce...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:10.3727/096504016X14685034103950

    authors: Lee SH,Hyun SK,Kim HB,Kang CD,Kim SH

    更新日期:2016-10-27 00:00:00

  • Contrasting patterns of DNA fragmentation induced by thymidylate synthase inhibitors, ZD1694 and AG-331.

    abstract::The patterns of DNA fragmentation were evaluated following a brief exposure (2 h) of the human ileocecal adenocarcinoma cell line, HCT-8, to several specific thymidylate synthase inhibitors, a quinazoline (ZD1694) and benz[cd]indole-containing molecule (AG-331). The magnitude and size of DNA fragmentation induced by t...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:

    authors: Panadero A,Yin MB,Voigt W,Rustum YM

    更新日期:1995-01-01 00:00:00

  • Prognostic Value of EGFR Expression for Patients with Stage III Colorectal Cancer Receiving Fluoropyrimidine Metronomic Maintenance Therapy After Radical Resection and Adjuvant Oxaliplatin-Based Chemotherapy.

    abstract::This study evaluated the survival effects of metronomic maintenance therapy with oral fluoropyrimidine in patients with stage III colorectal cancer (CRC) according to epidermal growth factor receptor (EGFR) expression. We enrolled 197 patients with stage III CRC who had undergone radical resection and FOLFOX regimen a...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:10.3727/096504020X15986099915822

    authors: Huang CW,Ma CJ,Su WC,Chen YT,Tsai HL,Yeh YS,Chang TK,Hsu WH,Yu FJ,Wang JY

    更新日期:2020-08-28 00:00:00

  • Resistance to inhibitors of S-adenosyl-L-homocysteine hydrolase in C1300 murine neuroblastoma tumor cells is associated with increased methionine adenosyltransferase activity.

    abstract::Adaptive changes occurring in C1300 murine neuroblastoma cell lines developed for resistance to nucleoside analogue inhibitors of S-adenosyl-L-homocysteine hydrolase (AdoHcyase, EC 3.3.1.1) were investigated. Two drug-resistant cell lines, rMNB-MDL-7-2 and rMNB-Deaz-7-2, were established from wild-type C1300 neuroblas...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:

    authors: Hamre MR,Clark SH,Mirkin BL

    更新日期:1995-01-01 00:00:00

  • DMBA/TPA-induced tumor formation is aggravated in human papillomavirus type 16 E6/E7 transgenic mouse skin.

    abstract::Human papillomavirus type 16 (HPV16) is a major causative factor in the development of uterine cervical carcinomas. We investigated the role of E6/E7 in tumor formation. Skin-specific E6/E7 transgenic mice showed approximately twice as many tumors compared with nontransgenic mice in dimethylbenz[a]anthracene (DMBA)-in...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:10.3727/000000006783980964

    authors: Kim MO,Kim SH,Shin MJ,Yu DH,Kim BS,Chang KT,Lee S,Park YB,Lee TH,Ryoo ZY

    更新日期:2007-01-01 00:00:00

  • Clinical studies with EO9, a new indoloquinone bioreductive alkylating cytotoxic agent. EORTC Early Clinical Trials Group.

    abstract::EO9 [3-hydroxy-5-aziridinyl-1-methyl-2-(1H-indole-4,7-indione)-prop-be ta- en-alpha-ol] is a new bioreductive alkylating indoloquinone with a distinct antitumor activity against solid tumors, excellent activity under hypoxic conditions, and lack of bone marrow toxicity in preclinical models. Clinical phase I studies w...

    journal_title:Oncology research

    pub_type: 临床试验,杂志文章

    doi:

    authors: Verweij J,Aamdal S,Schellens J,Koier I,Lund B

    更新日期:1994-01-01 00:00:00

  • Characterization of a novel immunocytolytic factor secreted by pancreatic adenocarcinoma.

    abstract::We observed a putative immunocytolytic factor secreted in the supernatant of several pancreatic adenocarcinoma cell lines that induces apoptosis in lymphocytes. A marked reduction in the viability of the target splenocytes was evident after coincubation with the supernatants from various pancreatic adenocarcinoma cell...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:

    authors: Divino CM,Angel LP,Brower ST,Chen SH

    更新日期:1999-01-01 00:00:00

  • Knockdown of HVEM, a Lymphocyte Regulator Gene, in Ovarian Cancer Cells Increases Sensitivity to Activated T Cells.

    abstract::Ovarian cancer is highly malignant with a gradually increasing incidence and a high mortality rate. Immunosuppression is induced in ovarian cancer, although the mechanism detail is not clear. It has been indicated that HVEM (herpesvirus entry mediator) B- and T-lymphocyte attenuator (BTLA) negatively regulates the imm...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:10.3727/096504016X14641336229602

    authors: Zhang T,Ye L,Han L,He Q,Zhu J

    更新日期:2016-01-01 00:00:00

  • Microenvironment analysis of prognosis and molecular signature of immune-related genes in lung adenocarcinoma.

    abstract::There is growing evidence on the clinical significance of Tumor Microenvironment (TME) cells in predicting prognosis and therapeutic effects. However, cell interactionsin tumor microenvironments have not been thoroughly studied or systematicallyanalyzed so far. In this study, 22 immune cell components in the lung aden...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:10.3727/096504020X15907428281601

    authors: Ling B,Huang Z,Huang S,Qian L,Li G,Tang Q

    更新日期:2020-05-29 00:00:00

  • Exosomal miR-1228 From Cancer-Associated Fibroblasts Promotes Cell Migration and Invasion of Osteosarcoma by Directly Targeting SCAI.

    abstract::Cancer-associated fibroblasts (CAFs) play a predominant role in regulating tumor progression. Understanding how CAFs communicate with osteosarcoma is crucial for developing novel approaches for osteosarcoma therapy. Exosomes are able to transmit messages between cells. In this study, we demonstrated that CAFs transfer...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:10.3727/096504018X15336368805108

    authors: Wang JW,Wu XF,Gu XJ,Jiang XH

    更新日期:2019-09-23 00:00:00

  • Bone marrow-derived progenitor cells could modulate pancreatic cancer tumorigenesis via peritumoral microenvironment in a rat model.

    abstract::Metaplastic tubular complexes (MTC) have been proposed as precursor lesions for pancreatic adenocarcinoma (PDAC). In this study, we investigated the potential role of bone marrow-derived progenitor cells (BMPC) in the formation of MTC and PDAC in a rat model. F344 rats defective for CD26 (dipeptidyl peptidase IV, DPPI...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:10.3727/096504009788428424

    authors: Pan JJ,Oh SH,Lee WC,Petersen BE

    更新日期:2009-01-01 00:00:00

  • miR-767-3p Inhibits Growth and Migration of Lung Adenocarcinoma Cells by Regulating CLDN18.

    abstract::Claudin18 (CLDN18) is necessary for intercellular junctions and is reported to be involved in cell migration and metastasis, making it like an oncogene in various cancer types. However, the biological function and regulatory mechanisms of CLDN18 in lung adenocarcinoma are not yet clear. In this study, we found downreg...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:10.3727/096504017X15112639918174

    authors: Wan YL,Dai HJ,Liu W,Ma HT

    更新日期:2018-05-07 00:00:00

  • The importance of release of proinflammatory cytokines, ROS, and NO in different stages of colon carcinoma growth and metastasis after treatment with cytotoxic drugs.

    abstract::In colorectal cancers, the local cytokine network and the levels of nitric oxide (NO) and reactive oxygen species (ROS) are known to be closely related to cancer progression and metastasis, but the influence of the currently administered therapies on the cancer microenvironment is not completely understood. We analyze...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:10.3727/096504010x12671222663593

    authors: Paduch R,Kandefer-Szerszeń M,Piersiak T

    更新日期:2010-01-01 00:00:00

  • The effect of acquired cisplatin resistance on sensitivity to EGFR tyrosine kinase inhibitors in EGFR mutant lung cancer cells.

    abstract::Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are used as first-line agents for treating nonsquamous cell lung cancer with EGFR mutation, there are many patients who have to receive these drugs following platinum-based chemotherapy. This study was designed to define whether exposure ...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:10.3727/096504012x13285365944337

    authors: Rho JK,Choi YJ,Choi YR,Kim SY,Choi SJ,Choi CM,Na II,Lee JC

    更新日期:2011-01-01 00:00:00

  • Decreased Expression of miR-138-5p by lncRNA H19 in Cervical Cancer Promotes Tumor Proliferation.

    abstract::MicroRNAs (miRNAs) play important roles in the carcinogenesis of cervical cancer. However, the expression and underlying mechanisms of miRNA in cervical cancer progression remain unclear. In the present study, our data showed that the expression of miR-138-5p was significantly downregulated in cervical cancer tissues,...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:10.3727/096504017X15017209042610

    authors: Ou L,Wang D,Zhang H,Yu Q,Hua F

    更新日期:2018-04-10 00:00:00

  • Heme Oxygenase-1 Inhibits Tumor Metastasis Mediated by Notch1 Pathway in Murine Mammary Carcinoma.

    abstract::Heme oxygenase-1 (HO-1) plays an important role in the progression of several malignancies including breast cancer. However, its role in breast cancer metastasis is still ambiguous. In this study, we observed the effect of HO-1 on mouse mammary carcinoma metastasis using the in vivo tumor metastasis model. Our results...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:10.3727/096504018X15415906335771

    authors: Li Q,Liu Q,Cheng W,Wei H,Jiang W,E F,Yu Y,Jin J,Zou C

    更新日期:2019-06-21 00:00:00

  • Tumor MET expression may not predict the risk of venous thromboembolism in cancer patients.

    abstract::Venous thromboembolism (VTE) occurs at an increased incidence in cancer patients. A cancer-related hypercoagulable state has been considered to play role in this phenomenon. Preclinical data suggest an association between tumor expression of MET proto-oncogene (MET) and a hypercoagulable state, resulting in VTE. We in...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:10.3727/096504010x12828372551786

    authors: Sayar H,Bunning JT,Bocklage TJ,Lee SJ,Libby E,Rabinowitz I

    更新日期:2010-01-01 00:00:00

  • Heterogeneous expression of DNA topoisomerase II alpha isoforms in tumor cell lines.

    abstract::DNA topoisomerase II alpha is a nuclear enzyme essential for DNA metabolism and cell cycle progression. Previous studies have shown that human tumor cell lines can express more than one topoisomerase II alpha isoform through alternative splicing. A 160-kDa isoform of topoisomerase II alpha has been described in severa...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:

    authors: Mo YY,Beck WT

    更新日期:1997-01-01 00:00:00

  • Toremifene enhances cell cycle block and growth inhibition by vinblastine in multidrug resistant human breast cancer cells.

    abstract::The clinical study of compounds that modulate multidrug resistance has been hindered by both the toxicities of these agents and the inability to monitor their effectiveness at the level of the tumor cell. Previously, toremifene has been shown to be well tolerated clinically and to sensitize multidrug resistant cells t...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:

    authors: Baker WJ,Maenpaa JU,Wurz GT,Koester SK,Seymour RC,Emshoff VD,Wiebe VJ,DeGregorio MW

    更新日期:1993-01-01 00:00:00

  • secErbB4-26/549 antagonizes ligand-induced ErbB4 tyrosine phosphorylation.

    abstract::ErbB4 is a member of the ErbB family of receptor tyrosine kinases. Because of a paucity of appropriate pharmacologic tools, little is known about ErbB4 functions in vivo. In response to this need, we hypothesized that a recombinant form of the extracellular domain of ErbB4 would antagonize ligand-induced receptor tyro...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:10.3727/0965040042707907

    authors: Gilmore JL,Riese DJ 2nd

    更新日期:2004-01-01 00:00:00

  • MicroRNA-377 Downregulates Bcl-xL and Increases Apoptosis in Hepatocellular Carcinoma Cells.

    abstract::Aberrantly expressed microRNAs (miRNAs/miRs) and their role in cancer development have recently gained more attention. However, the potential role of miRNAs in hepatocellular carcinoma (HCC) remains largely unknown. In this study, we demonstrated that miR-377 was markedly downregulated in HCC cell lines and primary hu...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:10.3727/096504016X14719078133168

    authors: Ge H,Zou D,Wang Y,Jiang H,Wang L

    更新日期:2017-01-02 00:00:00

  • The ability of new sugar-modified derivatives of antitumor anthracycline, daunorubicin, to stimulate NAD(P)H oxidation in different cellular oxidoreductase systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase.

    abstract::Numerous data indicate that cellular oxidoreductases may be responsible for the cardiotoxic effects of antitumor anthracycline drugs as a consequence of the mediation by these agents of one-electron transfer from reduced nucleotides to atmospheric oxygen. This process is catalyzed primarily by NADH dehydrogenase, NADP...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:10.3727/0965040042380450

    authors: Pawłowska J,Priebe W,Paine MJ,Wolf CR,Borowski E,Tarasiuk J

    更新日期:2004-01-01 00:00:00

  • 9-[3-(2-Nitro-1-imidazolyl)propylamino]-1,2,3,4-tetrahydroacridine hydrochloride. A novel DNA-affinic hypoxic cell cytotoxin and radiosensitizer. Comparison with NLA-1.

    abstract::Electron-affinic compounds with strong DNA intercalating properties have demonstrated less than the expected radiosensitization due to restriction of their mobility along the DNA backbone and their lower extravascular diffusion in tumors. A 2-nitroimidazole linked 1,2,3,4-tetrahydroacridine derivative (THNLA-1) has be...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:

    authors: Papadopoulou MV,Rosenzweig HS,Doddi M,Bloomer WD

    更新日期:1994-01-01 00:00:00

  • Methionine dependence of tumor cells: programmed cell survival?

    abstract::A majority of tumor cell lines are considered to be "methionine-dependent" because of their inability to grow in culture when methionine is replaced by its precursor, homocysteine. We have previously shown that this phenotype is not due to the incapacity to synthesize methionine from homocysteine but rather to a defic...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:

    authors: Dumontet C,Roch AM,Quash G

    更新日期:1996-01-01 00:00:00

  • A comparison of the effects of aphidicolin and other inhibitors on topoisomerase II-directed cytotoxic drugs.

    abstract::We have compared the effects of a number of inhibitors including aphidicolin, 2,4-dinitrophenol (DNP) and novobiocin on the in vitro cytotoxicity of several topoisomerase II (topo II)-directed agents, using cultured murine Lewis lung carcinoma cells. These agents comprised amsacrine, CI-921 (9-[(2-methoxy-4-methylsulf...

    journal_title:Oncology research

    pub_type: 杂志文章

    doi:

    authors: Haldane A,Finlay GJ,Baguley BC

    更新日期:1993-01-01 00:00:00