RESISTANCE TO FAS‐MEDIATED APOPTOSIS IN MALIGNANT TUMOURS IS RESCUED BY KN‐93 AND CISPLATIN VIA DOWNREGULATION OF c‐FLIP EXPRESSION AND PHOSPHORYLATION (English)

Clinical and Experimental Pharmacology and Physiology

The purpose of the present study was to investigate the molecular mechanisms that control tumour cell resistance and to search for molecules that could overcome Fas ligand (FasL) or CH‐11 resistance in certain tumours, including glioma and melanoma.

Twelve tumour cell lines were examined for their sensitivity to CH‐11‐induced apoptosis and then two of each of the CH‐11‐sensitive and ‐resistant tumour cell lines were analysed for Fas‐mediated death‐inducing signalling complex (DISC). The calmodulin kinase II (CaMKII) inhibitor KN‐93 and the chemotherapeutic drug cisplatin were used to treat resistant cells; the effects of these two drugs on CH‐11‐resistant tumour cells were investigated.

In CH‐11‐sensitive tumour cells, apoptosis‐initiating caspase 8 and caspase 10 were recruited to the DISC, where they became activated through autocatalytic cleavage, leading to apoptosis through cleavage of downstream substrates, such as caspase 3 and DNA fragmentation factor 45.

In CH‐11‐resistant cells, cellular Fas‐associated death domain‐like interleukin‐1b‐converting enzyme inhibitory protein (c‐FLIP) proteins were recruited to the DISC, resulting in inhibition of caspase 8 and caspase 10 cleavage. The c‐protein expression and phosphorylation of FLIP and CaMKII protein and enzyme activity were upregulated in resistant cells. Treatment of resistant cells with 100 mmol/L KN‐93 and 10 mg/mL cisplatin downregulated c‐FLIP expression, inhibited c‐FLIP phosphorylation and rescued CH‐11 sensitivity.

In conclusion, KN‐93 and cisplatin inhibit c‐FLIP protein expression and phosphorylation restores CH‐11‐induced apoptosis in tumour cells. tHe present study provides evidence for the use of a new combination therapeutic strategy in the treatment of malignant tumours.

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Table of contents – Volume 34, Issue 12

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Tables of content are generated automatically and are based on records of articles contained that are available in the TIB-Portal index. Due to missing records of articles, the volume display may be incomplete, even though the whole journal is available at TIB.

1221
INVOLVEMENT OF SOMATOSTATIN RECEPTOR SUBTYPES IN MEMBRANE ION CHANNEL MODIFICATION BY SOMATOSTATIN IN PITUITARY SOMATOTROPES
Yang, Seung‐Kwon / Chen, Chen | 2007
1228
UPREGULATED ENDOTHELIN SYSTEM IN DIABETIC VASCULAR DYSFUNCTION AND EARLY RETINOPATHY IS REVERSED BY CPU0213 AND TOTAL TRITERPENE ACIDS FROM FRUCTUS CORNI
Su, Wei / Dai, De‐Zai / Liu, Hao‐Ran / Na, Tao / Dai, Yin | 2007
1234
PROTECTIVE EFFECTS OF MAGNESIUM AGAINST ISCHAEMIA–REPERFUSION INJURY THROUGH INHIBITION OF P‐SELECTIN IN RATS
Ying, Shu‐Qin / Fang, Lu / Xiang, Mei‐Xiang / Xu, Geng / Shan, Jiang / Wang, Jian‐An | 2007
1240
OATP1B1 POLYMORPHISM IS A MAJOR DETERMINANT OF SERUM BILIRUBIN LEVEL BUT NOT ASSOCIATED WITH RIFAMPICIN‐MEDIATED BILIRUBIN ELEVATION
Zhang, Wei / He, Yi‐Jing / Gan, Zhou / Fan, Lan / Li, Qing / Wang, An / Liu, Zhao‐Qian / Deng, Sheng / Huang, Yuan‐Fei / Xu, Lin‐Yong et al. | 2007
1245
RESISTANCE TO FAS‐MEDIATED APOPTOSIS IN MALIGNANT TUMOURS IS RESCUED BY KN‐93 AND CISPLATIN VIA DOWNREGULATION OF c‐FLIP EXPRESSION AND PHOSPHORYLATION
Yang, Bao‐Feng / Xiao, Chang / Li, Hong / Yang, Shi‐Jie | 2007
1252
REVERSAL OF CISPLATIN‐INDUCED CARNITINE DEFICIENCY AND ENERGY STARVATION BY PROPIONYL‐l‐CARNITINE IN RAT KIDNEY TISSUES
Aleisa, Abdulaziz M / Al‐Majed, Abdulhakeem A / Al‐Yahya, Abdulaziz A / Al‐Rejaie, Salim S / Bakheet, Saleh A / Al‐Shabanah, Othman A / Sayed‐Ahmed, Mohamed M | 2007
1260
ENDOTHELIUM‐TARGETED TRANSGENIC GTP‐CYCLOHYDROLASE I OVEREXPRESSION INHIBITS NEOINTIMA FORMATION IN MOUSE CAROTID ARTERY
Liao, Song‐Jie / Lin, Li / Zeng, Jin‐Sheng / Huang, Ru‐Xun / Channon, Keith M / Chen, Alex F | 2007
1267
INHIBITORY EFFECTS OF ENDOGENOUS l‐ARGININE ANALOGUES ON NITRIC OXIDE SYNTHESIS IN PLATELETS: ROLE IN PLATELET HYPERAGGREGABILITY IN HYPERTENSION
De Meirelles, Luisa R / Mendes‐Ribeiro, Antônio C / Santoro, Marcelle M / Mendes, Michely AP / Da Silva, Michele NSB / Mann, Giovanni E / Brunini, Tatiana MC | 2007
1272
EFFECT OF THE HEME OXYGENASE INDUCER HEMIN ON BLOOD HAEMOSTASIS MEASURED BY HIGH‐FREQUENCY ULTRASOUND
Rochefort, Gaël Y / Libgot, Rachel / Desbuards, Nicolas / Schlecht, Deborah / Halimi, Jean‐Michel / Ossant, Frederic / Eder, Veronique / Antier, Daniel | 2007
1276
Gαq‐PROTEIN CARBOXYL TERMINUS IMITATION POLYPEPTIDE GCIP‐27 ATTENUATES CARDIAC HYPERTROPHY IN VITROAND IN VIVO
Zhang, Hai‐Gang / Li, Xiao‐Hui / Zhou, Jian‐Zhi / Liu, Ya / Jia, Yi / Yuan, Zhi‐Bing | 2007
1276
Gaq-PROTEIN CARBOXYL TERMINUS IMITATION POLYPEPTIDE GCIP-27 ATTENUATES CARDIAC HYPERTROPHY IN VITRO AND IN VIVO
Zhang, H. G. / Li, X. H. / Zhou, J. Z. / Liu, Y. / Jia, Y. / Yuan, Z. B. | 2007
1282
EXPRESSION OF P2X PURINOCEPTORS IN PC12 PHAEOCHROMOCYTOMA CELLS
Sun, Ji‐Hu / Cai, Guo‐Jun / Xiang, Zheng‐Hua | 2007
1287
ASSOCIATIONS BETWEEN 45T/G POLYMORPHISM OF THE ADIPONECTIN GENE AND PLASMA ADIPONECTIN LEVELS WITH TYPE 2 DIABETES
Li, Lin‐Lin / Kang, Xiao‐Long / Ran, Xin‐Jian / Wang, Ye / Wang, Chang‐Hui / Huang, Lin / Ren, Jun / Luo, Xin / Mao, Xin‐Min | 2007
1291
SYSTEMIC PLASMA LEVELS OF NITRITE/NITRATE (NOX) REFLECT BRACHIAL FLOW‐MEDIATED DILATION RESPONSES IN YOUNG MEN AND WOMEN
Casey, Darren P / Beck, Darren T / Braith, Randy W | 2007
1294
CHRONIC SUPPLEMENTATION OF CREATINE AND VITAMINS C AND E INCREASES SURVIVAL AND IMPROVES BIOCHEMICAL PARAMETERS AFTER DOXORUBICIN TREATMENT IN RATS
Santos, Ronaldo VT / Batista, Miguel L Jr / Caperuto, Érico C / Costa Rosa, Luis FBP | 2007
1300
PRESERVATION OF MECHANICAL AND ENERGETIC FUNCTION AFTER ADENOVIRAL GENE TRANSFER IN NORMAL RAT HEARTS
Sakata, Susumu / Liang, Lifan / Sakata, Naoya / Sakata, Yuri / Chemaly, Elie R / Lebeche, Djamel / Takewa, Yoshiaki / Chen, Jiqiu / Park, Woo Jin / Kawase, Yoshiaki et al. | 2007
1307
CELLULAR DISTRIBUTION OF THE RENAL BUMETANIDE‐SENSITIVE Na–K–2Cl COTRANSPORTER BSC‐1 IN THE INNER STRIPE OF THE OUTER MEDULLA DURING THE DEVELOPMENT OF HYPERTENSION IN THE SPONTANEOUSLY HYPERTENSIVE RAT
Sonalker, Prajakta A / Tofovic, Stevan P / Jackson, Edwin K | 2007
1313
FUNCTIONAL INTERACTION BETWEEN DPI 201‐106, A DRUG THAT MIMICS CONGENITAL LONG QT SYNDROME, AND SEVOFLURANE ON THE GUINEA‐PIG CARDIAC ACTION POTENTIAL
Kang, Jiesheng / Chen, Xiao‐Liang / Reynolds, William P / Rampe, David | 2007
1317
DECREASED THRESHOLD FOR THE NITRIC OXIDE DONOR GLYCERYL TRINITRATE IN CORTISOL‐INDUCED HYPERTENSION IN HUMANS
Kelly, JJ / Tam, SH / Williamson, PM / Whitworth, JA | 2007
1319
DETECTION OF PERIVASCULAR BLOOD FLOW IN VIVO BY CONTRAST‐ENHANCED INTRACORONARY ULTRASONOGRAPHY AND IMAGE ANALYSIS: AN ANIMAL STUDY
Vavuranakis, Manolis / Papaioannou, Theodore G / Kakadiaris, Ioannis A / O'Malley, Sean M / Naghavi, Morteza / Filis, Konstantinos / Sanidas, Elias A / Papalois, Apostolos / Stamatopoulos, Ilias / Stefanadis, Christodoulos | 2007
1324
REFEREES
| 2007
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CONTENTS
| 2007

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