Requirement of c-Jun N-Terminal Kinase for Apoptotic Cell Death Induced by Farnesyltransferase Inhibitor, Farnesylamine, in Human Pancreatic Cancer Cells

Mizukami, Yusuke; Ura, Hideki; Obara, Takao; Habiro, Atsuya; Izawa, Tsutomu; Osanai, Manabu; Yanagawa, Nobuyuki; Tanno, Satoshi; Kohgo, Yutaka

doi:10.1006/bbrc.2001.5744

Cited by 17 publications

(6 citation statements)

References 42 publications

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“…The notion that FTIs may have different effects in transformed cells when compared to untransformed cells is further confirmed by the inhibition of JNK activation. Whereas Mizukami et al (20) see JNK activation in response to FTI in transformed cells, we observed diminished JNK activation in FTI-treated untransformed cells. With regard to the therapeutic application of FTIs, it is important to note that the enhanced cytokine production in FTItreated cells might lead to averse events with respect to allergic responses (but may be beneficial in immunocompromised patients).…”

Section: Discussioncontrasting

confidence: 99%

Farnesyl Protein Transferase Inhibition Interferes with Activation of MAP Kinase Family Members in Human Peripheral Blood Monocytes

Vervenne

Bos

Rens

et al. 2002

Mol Med

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Background: Farnesyl protein transferase inhibitors have emerged as promising novel agents for combating cancerous disease. Nevertheless, the importance for farnesyl protein transferase enzymatic activity for cellular physiology of untransformed cells remains poorly investigated. Materials and Methods: Peripheral blood monocytes, isolated from the blood of eight healthy volunteers, were treated with a farnesyl protein transferase inhibitor (FTI 744,832) or vehicle control for 16 hr. Subsequently cells were challenged with different concentrations of lipopolysaccharide (LPS), colony stimulating factor-1 (CSF-1), or phorbol esters for 10 min, after which the activation state of p42/p44 MAP kinase, p38 MAP kinase, and Jun-N-terminal kinase was investigated using Western blotting and phosphospecific antibodies.

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Section: Discussioncontrasting

confidence: 99%

Farnesyl Protein Transferase Inhibition Interferes with Activation of MAP Kinase Family Members in Human Peripheral Blood Monocytes

Vervenne

Bos

Rens

et al. 2002

Mol Med

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“…H 2 O 2 has been demonstrated to induce oxidative stresses, cellular injury and apoptosis through JNK pathways (Mizukami et al, 2001). Activation of JNK by oxidant stress is initiated in the mitochondria and involves ROS generation (Dougherty et al, 2004).…”

Section: Baicalein Decreased Jnk Phosphorylation Induced By H 2 O 2 Ementioning

confidence: 99%

Baicalein Protects Cardiomyocytes Against Mitochondrial Oxidant Injury Associated with JNK Inhibition and Mitochondrial Akt Activation

Huang

Shao

et al. 2014

Am. J. Chin. Med.

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Baicalein, a flavonoid derived from Scutellaria baicalensis Georgi, possesses cardioprotection against oxidant injury by scavenging reactive oxygen species (ROS). Few studies investigate whether baicalein protection is mediated by attenuating mitochondrial ROS and modulating the prosurvival and proapoptotic signaling. Primary cultured chick cardiomyocytes were used to study the role of baicalein in mitochondrial superoxide [Formula: see text] generation and signaling of Akt and JNK. Cells were exposed to H 2 O 2 for 2 h and baicalein was given 2 h prior to and during 2 h of H 2 O 2 exposure. Cell viability was assessed by propidium iodide and DNA fragmentation. H 2 O 2 (500 μM) significantly induced 45.3 ± 6.2% of cell death compared to the control (p < 0.001) and resulted in DNA laddering. Baicalein (10, 25 or 50 μM) dose-dependently reduced the cell death to 38.7 ± 5.6% (p = 0.226); 31.2 ± 3.9% (p < 0.01); 30.3 ± 5.3% (p < 0.01), respectively. It also attenuated DNA laddering. Further, baicalein decreased intracellular ROS and mitochondrial [Formula: see text] generation that was confirmed by superoxide dismutase PEG-SOD and mitochondria electron transport chain complex III inhibitor stigmatellin. In addition, baicalein increased Akt phosphorylation and decreased JNK phosphorylation in H 2 O 2-exposed cells. Moreover, baicalein augmented mitochondrial phosphorylation of Akt Thr308 and GSK3β Ser9, and prevented mitochondrial cytochrome c release assessed by cellular fractionation. Our results suggest that baicalein cardioprotection may involve an attenuation of mitochondrial [Formula: see text] and an increase in mitochondrial phosphorylation of Akt and GSK3β while decreasing JNK activation.

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“…17 Distinctive from the multivalent regulation of the reductase activity consisting of sterol-mediated transcriptional feedback inhibition and nonsterol-mediated and particularly farnesol-mediated posttranscriptional ablation in sterologenic tissues, tumor reductase is resistant to sterol feedback regulation but retains a unique sensitivity to the non-sterolYmediated down-regulation. Consequently, farnesol suppresses the proliferation of human MIA PaCa-2, PK-1, PK-9, and BxPC-3 pancreatic tumor cells, 18,19 human DU145 and PC-3 prostate tumor cells, 20,21 human A549 and H460 lung carcinoma cells, 22Y24 human HL-60 leukemia cells, 25 C-4-1 cervical carcinoma cells, 20 and murine B16 melanoma cells. 26Y28 Dietary farnesol at doses nontoxic to host animals suppresses the growth of implanted pancreatic ductal adenocarcinomas in Syrian Golden hamster 18,29 and chemically initiated hepatocarcinogenesis 30 and colorectal carcinogenesis 31 in rats.…”

mentioning

confidence: 99%

d-δ-Tocotrienol-Mediated Suppression of the Proliferation of Human PANC-1, MIA PaCa-2, and BxPC-3 Pancreatic Carcinoma Cells

Hussein

2009

Pancreas

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Requirement of c-Jun N-Terminal Kinase for Apoptotic Cell Death Induced by Farnesyltransferase Inhibitor, Farnesylamine, in Human Pancreatic Cancer Cells

Cited by 17 publications

References 42 publications

Farnesyl Protein Transferase Inhibition Interferes with Activation of MAP Kinase Family Members in Human Peripheral Blood Monocytes

Farnesyl Protein Transferase Inhibition Interferes with Activation of MAP Kinase Family Members in Human Peripheral Blood Monocytes

Baicalein Protects Cardiomyocytes Against Mitochondrial Oxidant Injury Associated with JNK Inhibition and Mitochondrial Akt Activation

d-δ-Tocotrienol-Mediated Suppression of the Proliferation of Human PANC-1, MIA PaCa-2, and BxPC-3 Pancreatic Carcinoma Cells

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