Enhancement of tumor growth by drugs with some common molecular actions

LaBella, Frank S.; Brandes, Lorne J.

doi:10.1002/(sici)1098-2744(199606)16:2<68::aid-mc2>3.0.co;2-j

Cited by 21 publications

(10 citation statements)

References 73 publications

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“…More recently, Nebert proposed that P450 enzymes control the levels of endogenous lipid mediators that, in turn, modulate gene function, including expression of P450 isozymes themselves [Nebert, 1991]. On the basis of our findings, we suggest that intracellular HA regulates the catalytic activity of P450 enzymes, and that intracellular PA and various arylalkyl-amine drugs that modulate normal and neoplastic growth, including certain antidepressants [Brandes et al, 1992a], H 1 -antihistamines [Brandes et al, 1994], the antiestrogen tamoxifen [LaBella and Brandes, 1996], and the antiandrogen, flutamide [Brandes et al, 1997], perturb the HA/P450 interaction and reset the steady state levels of eicosanoids and other lipids involved in growth regulation.…”

Section: Discussionsupporting

confidence: 62%

“…Evidence that a proportion of microsomal H IC sites represents HA binding to cytochrome P450 enzymes derives from the following: (1) in liver and adrenal microsomes, HA generates a P450 absorbance spectrum typical of ligands that bind directly to the heme iron atom ; (2) thioperamide, an imidazole antagonist of H 3 receptors [Arrang et al, 1983], yields a P450 absorbance difference spectrum and inhibits HA binding to adrenal P450 (K s ϭ 0.3 µM), competes for 3 H-HA binding in the same preparation (K i ϭ 0.3 µM), and inhibits cortisol secretion from isolated adrenal cortical cells (IC 50 ϭ 0.2 µM) , suggesting both a physiological role for intracellular HA to modulate, and for thioperamide to antagonize, P450 mono-oxygenases that generate steroids; (3) the potencies of certain H 1 antihistamines, antidepressants, antiestrogens, and other drugs to inhibit lymphocyte mitogenesis in vitro and to stimulate experimental tumor growth in vitro and in vivo, correlate with potencies to inhibit 3 H-HA binding in microsomes, the HA/P450 absorbance complex, and P450 catalytic activity [Brandes et al, 1994;LaBella and Brandes, 1996].…”

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Potent interaction of histamine and polyamines at microsomal cytochrome P450, nuclei, and chromatin from rat hepatocytes

1998

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Histamine and polyamines have been implicated in the mediation of cell proliferation. Our previous work linked the growth-modulatory effects of histamine with its binding to intracellular sites in microsomes and nuclei of various tissues. In this study, we identify cytochrome P450 enzymes as a major component of microsomal intracellular sites in hepatocytes and demonstrate that polyamines compete with high affinity for histamine binding to them. Spectral measurement of histamine binding to P450 in liver microsomes resolved high and intermediate affinity binding sites (Ks1 = 2.4 +/- 1.6 microM; Ks2 = 90 +/- 17 microM) that corresponded to microsomal binding sites (Kd1 = 1.0 +/- 0.9 microM; Kd2 = 57 +/- 13 microM) resolved by 3H-histamine binding; additional low affinity (Kd3 approximately 3 mM), and probably physiologically irrelevant, sites were resolved only by 3H-histamine radioligand studies. As determined spectrally, treatment of microsomes with NADPH/carbon monoxide decreased histamine binding to P450 by about 90% and, as determined by 3H-histamine binding, abolished the high affinity sites and reduced by 85% the number of intermediate sites. Spermine competed potently for 3H-histamine binding: in microsomes, Ki = 9.8 +/- 5.8 microM; in nuclei, Ki = 13.7 +/- 3.1 microM; in chromatin, Ki = 46 +/- 33 nM. Polyamines inhibited the P450/histamine absorbance complex with the rank order of potency: spermine > spermidine >> putrescine. In contrast, histamine did not compete for 3H-spermidine binding in nuclei or microsomes, suggesting that polyamines modulate histamine binding allosterically. We propose that certain P450 isozymes that modulate gene function by controlling the level of oxygenated lipids, represent at least one common intracellular target of growth-regulatory endogenous bioamines and, as shown previously, of exogenous growth-modulatory drugs including antiestrogens, antiandrogens, and certain antidepressants and antihistamines.

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Section: Discussionsupporting

confidence: 62%

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confidence: 99%

Potent interaction of histamine and polyamines at microsomal cytochrome P450, nuclei, and chromatin from rat hepatocytes

1998

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“…In renal proximal tubule epithelium, AA is an important second messenger in signaling linked to epidermal growth factor (EGF), angiotensin II (Ang II), bradykinin, and other hormones. 2,3 Recently, AA and its lipoxygenase and cytochrome P450 derivatives have been implicated in mitogenesis [4][5][6] as well as in activation of mitogen-activated protein kinase (MAPK) cascade, 7,8 one of the most crucial pathways involved in induction of cell growth.…”

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confidence: 99%

Arachidonate-Induced Tyrosine Phosphorylation of Epidermal Growth Factor Receptor and Shc-Grb2-Sos Association

1998

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Abstract-Protein tyrosine phosphorylation induced by arachidonic acid (AA), an important lipid second messenger, was investigated in rabbit renal proximal tubule epithelial cells. AA stimulated tyrosine phosphorylation of a number of proteins with estimated molecular weights of 42, 44, 52, 56, 85, and 170/180 kDa. The phosphoproteins pp44 and pp42 were identified as 2 isoforms of mitogen-activated protein kinase (MAPK). Phosphorylation of MAPK in response to AA was transient, dose-dependent, and accompanied by an increase in its activity. The mechanism of AA-induced MAPK activation in RTE cells was protein kinase C-independent and involved tyrosine phosphorylation of adaptor protein Shc and its association with Grb2-Sos complex. Moreover, stimulation of RTE cells with AA resulted in significant phosphorylation of epidermal growth factor (EGF) receptor and its association with Shc. The effect of AA on EGF receptor phosphorylation, its association with Shc, and MAPK activation was similar to the effect of 1 ng/mL EGF. Tyrphostin AG1478, a specific inhibitor of EGF receptor tyrosine kinase activity, completely blocked the effects of AA and EGF but not phorbol ester on MAPK phosphorylation. These data suggest that in renal tubular epithelial cells, the mechanism of AA-induced MAPK activation involves tyrosine phosphorylation of EGF receptor and its association with Shc and Grb2-Sos complex. Given the critical role of AA in signaling linked to G protein-coupled receptors (GPCRs), these observations provide a mechanism for cross talk between GPCRs linked to phospholipases and the tyrosine kinase receptor signaling cascades. (Hypertension. 1998;32:1089-1093.)Key Words: kinases Ⅲ receptor, epidermal growth factor Ⅲ Shc Ⅲ phosphorylation Ⅲ kidney A rachidonic acid (AA) and its metabolites play a critical role in a variety of physiological and pathological processes within the kidney.1 It is released from phospholipids after activation of phospholipases in response to different extracellular signals linked to growth factors and G proteincoupled receptors. In renal proximal tubule epithelium, AA is an important second messenger in signaling linked to epidermal growth factor (EGF), angiotensin II (Ang II), bradykinin, and other hormones. 2,3 Recently, AA and its lipoxygenase and cytochrome P450 derivatives have been implicated in mitogenesis 4-6 as well as in activation of mitogen-activated protein kinase (MAPK) cascade, 7,8 one of the most crucial pathways involved in induction of cell growth.Activation of MAP kinase (extracellular signal regulated kinase [ERK]) requires its phosphorylation on tyrosine and threonine residues by MAP kinase kinase (MEK), which in turn is phosphorylated by the serine/threonine kinase, Raf. 9 This evolutionary conserved kinase cascade is a common pathway for both receptor tyrosine kinase-and G proteinmediated mitogenesis.10 Activation of Raf can be induced by different pathways involving protein kinase C (PKC)-dependent and -independent mechanisms. The latter involves tyrosine phosphoryla...

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“…Antidepressants are used to treat patients with depression and related disorders. Animal models and the findings of cell line studies suggested that some antidepressants may promote the growth of neoplasms; by contrast, other experimental studies reported that some antidepressants provide chemopreventive properties against colorectal cancer . Reported results from epidemiologic studies are inconclusive and are not always consistent with experimental study findings .…”

Section: Discussionmentioning

confidence: 96%

Does use of tetracyclic antidepressant—mirtazapine reduce cancer risk in depression patients?

Sun

Lin

Liang

et al. 2013

Pharmacoepidemiology and Drug

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Enhancement of tumor growth by drugs with some common molecular actions

Cited by 21 publications

References 73 publications

Potent interaction of histamine and polyamines at microsomal cytochrome P450, nuclei, and chromatin from rat hepatocytes

Potent interaction of histamine and polyamines at microsomal cytochrome P450, nuclei, and chromatin from rat hepatocytes

Arachidonate-Induced Tyrosine Phosphorylation of Epidermal Growth Factor Receptor and Shc-Grb2-Sos Association

Does use of tetracyclic antidepressant—mirtazapine reduce cancer risk in depression patients?

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