Tyrosine kinase inhibitors and signal transduction modulators: Rationale and current status as chemopreventive agents for prostate cancer

Bergan, Raymond C.; Waggle, D. H.; Carter, Stephen K.; Horak, Ivan D.; Slichenmyer, William J.; Meyers, Michael L.

doi:10.1016/s0090-4295(00)00946-8

Cited by 20 publications

(4 citation statements)

References 11 publications

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“…We also observed that PD153035 was able to induce an effective apoptotic death of LNCaP, DU145 and PC3 cells and that its cytotoxic effect could be potentiated in the presence of Rp‐cAMPs. This supports several previous works carried out with the antisense oligonucleotides, monoclonal antibodies or selective inhibitors targeting EGFR and/or PKA that indicated that the blockade of these signaling pathways resulted in an apoptotic death of several cancer cell types including PC cells13, 16, 27, 28, 29, 41, 42, 43, 44, 45, 46, 47, 48, 49 Specifically, the combination of EGFR and PKA inhibitors at suboptimal doses also caused a greater degree of apoptotic death than that observed with each single agent. It has also been observed that in vivo inoculation of curcumin or antisense oligonucleotide directed against EGFR into LNCaP and established PC3 tumor in nude mice was able to block the development of PCs 28, 48, 49…”

Section: Discussionsupporting

confidence: 90%

Synergistic antiproliferative and apoptotic effects induced by epidermal growth factor receptor and protein kinase a inhibitors in human prostatic cancer cell lines

Mimeault

Pommery

Hénichart

2003

Intl Journal of Cancer

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Our results revealed that the blockade of epidermal growth factor receptor (EGFR) tyrosine kinase and protein kinase A (PKA) signaling pathways by specific inhibitors (PD153035 and Rp-cAMPs) leads to a synergistic inhibition of EGF-and serum-stimulated growth of human prostatic cancer cells (LNCaP, DU145 and PC3) concomitant with an arrest in the G1 phase of cellular cycle. Of particular interest, the combination of PD153035 and Rp-cAMPs also caused a more substantial apoptotic/necrotic death of these prostatic cancer cells as compared to drugs alone. Moreover, we observed that the inhibition of acidic sphingomyelinase and caspase cascades results in a marked reduction of DNA fragmentation and apoptotic death induced by PD153035, alone or in combination with Rp-cAMPs, in EGF stimulated PC3 cells. This suggests that these agents might mediate their cytotoxic effects at least in part via the ceramide generation and activation of caspase signaling pathways. N-oleoylethanolamine (OE), an inhibitor of acidic ceramidase, consistently potentiated the apoptotic effects of PD153035 in all the prostatic cancer cell lines tested. Additionally, the cellular ceramide content estimated for PC3 cells was increased after treatment with PD153035, alone or in combination, at a lower dose with OE and Rp-cAMPs.The synergistic apoptotic effect of PD153035 plus Rp-cAMPs induced in PC3 was also accompanied by a significant rate of mitochondrial membrane depolarization and release of cytochrome c into cytosol as compared to drugs alone. Combined, the results indicated that the simultaneous inhibition of EGFR and PKA signaling cascades might lead to a more massive apoptotic death of metastatic prostatic cancer cells by increasing ceramide accumulation and activating of caspase cascade of a mitochondrial dependent manner. © 2003 Wiley-Liss, Inc. Key words: epidermal growth factor receptor; protein kinase A; growth inhibition; apoptosis; prostatic cancerThe prostatic cancers (PCs) are among the most common causes of death because no effective therapeutic treatment allows to abrogate the progression of localized PC to advanced and invasive forms of malignancies. [1][2][3][4][5][6][7] Although certain PC cells are sensitive to effects of androgen deprivation therapies and chemotherapy, other metastatic PC cell types have acquired multiple oncogenic phenotypes that confer them to resistance to ionizing radiations and to most of the anticarcinogenic agents. The development of PCs depends on the strict balance between the rate of proliferation and programmed cell death, also called apoptosis. EGFR and its ligands, EGF and transforming growth factor alpha (TGF␣), play a critical role during tumorigenesis of the prostate gland. [7][8][9][10][11][12][13] In general, it has been observed that the stimulation of EGFR by its ligands, through autocrine and paracrine pathways, leads to the activation of different signaling cascades involving mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI 3 K) response elements. The antia...

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Section: Discussionsupporting

confidence: 90%

Synergistic antiproliferative and apoptotic effects induced by epidermal growth factor receptor and protein kinase a inhibitors in human prostatic cancer cell lines

Mimeault

Pommery

Hénichart

2003

Intl Journal of Cancer

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“…Mimosine and Cancer Therapy. Cell growth and differentiation are the processes intimately associated with carcinogenesis and regulated by tyrosine kinases and other signaling proteins (176). Natural or synthesized agents that can inhibit cell cycle progression at specific points or the chemicals that affect DNA synthesis are potentially useful for the development of anticancer drugs and effective tools for the investigation of DNA metabolism.…”

Section: Saponinsmentioning

confidence: 99%

Potential Therapeutic Applications of Some Antinutritional Plant Secondary Metabolites

Singh

Bhat

Singh

2003

J. Agric. Food Chem.

222

149

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Plant-based formulations have been used since ancient times as remedial measures against various human and animal ailments. Over the past 20 years interest in traditional medicines has increased considerably in many parts of the world. Whereas modifications in lifestyles, including diet, have had a profound effect on the increased risks of various diseases, there is considerable scientific evidence, both epidemiological and experimental, regarding vegetables and fruits as key features of diets associated with reduced risks of diseases such as cancers and infections. This has led to the use of a number of phytometabolites as anticarcinogenic and cardioprotective agents, promoting a dramatic increase in their consumption as dietary supplements. There are changing perceptions regarding the therapeutic potential of various plant secondary metabolites (PSMs), some of which have also been known to possess certain antinutritional qualities. The knowledge gained at the cellular and molecular levels, and biological activities of PSMs including tannin-polyphenols, saponins, mimosine, flavonoids, terpenoids, and phytates, would be useful in planning for future epidemiological studies and human cancer prevention trials, especially when a large pure dosage is not the option to deliver the active compounds to many tissues. It is well observed that alteration of cell cycle regulatory gene expression is frequently found in tumor tissues or cancer cell lines, and studies have suggested that the herbal-based or plant-originated cell cycle regulators might represent a new set of potential targets for anticancer drugs. The recent upsurge of interest in this area of research and advances made therein indicate that the impact of a number of diseases affecting humans and animals may be lessened, if not prevented, by simple dietary intake of PSMs with putative therapeutic properties.

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“…[10] Recent studies have shown that this process can be pharmacologically reversed, [11][12][13] and that doing so represents an important pharmacologic endpoint in prostate cancer chemoprevention trials. [14,15] Drugs that reverse prostate cell detachment are now being tested in humans. [16] However, the genes responsible for regulating this process are essentially unknown.…”

Section: Introductionmentioning

confidence: 99%

A Simple Analysis of Gene Expression and Variability in Gene Arrays Based on Repeated Observations

Jovanovic

Huang

Liu

et al. 2001

American Journal of PharmacoGenomics

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Tyrosine kinase inhibitors and signal transduction modulators: Rationale and current status as chemopreventive agents for prostate cancer

Cited by 20 publications

References 11 publications

Synergistic antiproliferative and apoptotic effects induced by epidermal growth factor receptor and protein kinase a inhibitors in human prostatic cancer cell lines

Synergistic antiproliferative and apoptotic effects induced by epidermal growth factor receptor and protein kinase a inhibitors in human prostatic cancer cell lines

Potential Therapeutic Applications of Some Antinutritional Plant Secondary Metabolites

A Simple Analysis of Gene Expression and Variability in Gene Arrays Based on Repeated Observations

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