NADH: Ubiquinone Oxidoreductase Inhibitors Block Induction of Ornithine Decarboxylase Activity in MCF‐7 Human Breast Cancer Cells*

Jc, Rowlands; Je, Casida

doi:10.1111/j.1600-0773.1998.tb01471.x

Cited by 31 publications

(20 citation statements)

References 24 publications

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“…1A, rotenone dose-dependently increased histone-associated DNA fragmentation. However, dopaminergic SH-SY5Y cells are far more vulnerable to rotenone than breast cancer MCF-7 cells and hepatoma HepG2 cells despite the fact that rotenone inhibits mitochondrial complex I in these cells and produces ROS (Rowlands and Casida, 1998;Greenamyre et al, 2003). We also ascertained that apoptosis of SH-SY5Y cells was induced by rotenone using another technique.…”

Section: Resultsmentioning

confidence: 89%

Mitochondrial Complex I Inhibitor Rotenone-Elicited Dopamine Redistribution from Vesicles to Cytosol in Human Dopaminergic SH-SY5Y Cells

Watabe¹,

Nakaki²

2007

J Pharmacol Exp Ther

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Parkinson's disease is a chronic neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra. Rotenone, a pesticide, produces selective degeneration of dopaminergic neurons and motor dysfunction in rats. To determine the mechanisms underlying rotenoneinduced neuronal death, we investigated whether intracellular dopamine plays a role in rotenone (0.1-0.4 M)-induced apoptosis, using an in vitro model of human dopaminergic SH-SY5Y cells. The 40% decrease of dopamine content by inhibition of dopamine synthesis suppressed rotenoneinduced apoptosis. On the other hand, the 30% increase of dopamine content by inhibition of dopamine metabolism enhanced rotenone-induced apoptosis. Depletion of intracellular dopamine using reserpine (0.1-10 M) also prevented rotenone-induced apoptosis, and this effect was counteracted by dopamine (10 -100 M) replenishment. Inhibition of dopamine reverse transport increased cytosolic dopamine and enhanced rotenone-induced apoptosis. We examined the intracellular localization of dopamine in rotenone-treated cells immunocytochemically and quantitatively. Rotenone induced dopamine redistribution from vesicles to the cytosol. In this process, rotenone stimulated reactive oxygen species and protein carbonylation and decreased an antioxidant, glutathione. Addition of an antioxidant, N-acetylcysteine (3 mM), prevented dopamine being expelled from vesicles and inhibited rotenone-induced apoptosis. Our findings demonstrate that rotenone-generated reactive oxygen species are involved in dopamine redistribution to the cytosol, which in turn may play a role in rotenone-induced apoptosis of dopaminergic cells.Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by progressive loss of dopamine neurons in the substantia nigra, decreased striatal dopamine level, and consequent motor dysfunction (Dawson and Dawson, 2003). The etiology of the nigral dopamine neuronal degeneration is unknown, although both genetic mutations and environmental factors have been identified as contributing to certain forms of this disorder (Shastry, 2001). An established hallmark of PD is a reduction in the activity of brain mitochondrial enzyme complex I (Schapira et al., 1990). Complex I inhibitors, such as 1-methyl-4-phenylpyridinium ion (MPP ϩ ) and rotenone, have been shown to cause apoptosis of nigral dopaminergic neurons and parkinsonian dysfunction (Heikkila et al., 1985;Forno et al., 1993;Greenamyre et al., 2001;Ayala et al., 2007). Poly-(ADP-ribose) polymerase-1 (PARP-1) is involved in MPP ϩ -induced apoptosis and efficacious effects of PARP-1 inhibitors have been demonstrated in a PD model using MPP ϩ , although the role of PARP-1 in the pathogenesis of PD is unclear (Outeiro et al., 2007). These observations suggest that a defect in mitochondrial complex I activity may contribute to the neurodegenerative process in PD. These dopaminergic neurotoxins enhance production of reactive oxygen species (ROS) in mitochondria, but much less is known about ho...

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Section: Resultsmentioning

confidence: 89%

Mitochondrial Complex I Inhibitor Rotenone-Elicited Dopamine Redistribution from Vesicles to Cytosol in Human Dopaminergic SH-SY5Y Cells

Watabe¹,

Nakaki²

2007

J Pharmacol Exp Ther

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“…Similarly, oxygen consumption by intact cells was inhibited by short-term exposures to ATRA, 114 phenyethyl isothiocyanate, 207 CD437, 114 4HPR, 115 deguelin, 117 rotenone, 118 capsaicin, 116 and resiniferatoxin. 116 The interruption of biochemical processes associated with OXPHOS (e.g., substrate oxidation, oxygen consumption, the maintenance of m , ATP synthesis, or ATP/ADT exchange) has been reported in isolated mitochondria and/or submitochondrial particles exposed to ATRA, 131 curcumin, 155 benzyl isothiocyanate, 208 tamoxifen, 125,209 genistein, 126 resveratrol, 126 capsaicin, 129,204,205 deguelin, 126,210,211 and rotenone. 126,129,210,211 Mitochondrial swelling has been observed in isolated mitochondria exposed to CD437 212 curcumin, 155,213 and benzyl isothiocyanate.…”

Section: Class Agent Proposed Mechanismsmentioning

confidence: 98%

Mitochondria: A novel target for the chemoprevention of cancer

Hail¹

2005

Apoptosis

100

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The mitochondria have emerged as a novel target for anticancer chemotherapy. This tenet is based on the observations that several conventional and experimental chemotherapeutic agents promote the permeabilization of mitochondrial membranes in cancerous cells to initiate the release of apoptogenic mitochondrial proteins. This ability to engage mitochondrial-mediated apoptosis directly using chemotherapy may be responsible for overcoming aberrant apoptosis regulatory mechanisms commonly encountered in cancerous cells. Interestingly, several putative cancer chemopreventive agents also possess the ability to trigger apoptosis in transformed, premalignant, or malignant cells in vitro via mitochondrial membrane permeabilization. This process may occur through the regulation of Bcl-2 family members, or by the induction of the mitochondrial permeability transition. Thus, by exploiting endogenous mitochondrial-mediated apoptosis-inducing mechanisms, certain chemopreventive agents may be able to block the progression of premalignant cells to malignant cells or the dissemination of malignant cells to distant organ sites as means of modulating carcinogenesis in vivo. This review will examine cancer chemoprevention with respect to apoptosis, carcinogenesis, and the proapoptotic activity of various chemopreventive agents observed in vitro. In doing so, I will construct a paradigm supporting the notion that the mitochondria are a novel target for the chemoprevention of cancer.

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“…Complex I inhibitors rotenone, piericidin A, and amytal have been used in co-treatment with DES and/or estrogens to elucidate the site of estrogen action on electron transfer [28,39]. In MCF7 cells, it was demonstrated that co-treatment with rotenone (10 nM) and E2 (10 nM) strongly inhibited ornithine decarboxylase activity by 86% [42]. More recently, a study reported that treatment with 10 μM of 2-methoxyestradiol (2-Me) induced apoptosis in Ewing sarcoma cells through hydrogen peroxide (H 2 O 2 ) production [43].…”

Section: Introductionmentioning

confidence: 99%

“…Evidence in support of a ROS signal transduction pathway originating from complex I comes from a study which reported that the mitochondrial complex I inhibitor, rotenone, blocked ROS mediated signaling. Interestingly, this study demonstrated that a co-treatment of rotenone (10 nM) and E2 (10 nM) inhibited ornithine decarboxylase activity by 86% in MCF7 cells [42]. Since ornithine decarboxylase activity is a marker for cell growth, it appears that a signal transduction pathway for estrogen-induced cell growth may originate from the mitochondria assuming that rotenone inhibition is specific to complex I.…”

Section: Introductionmentioning

confidence: 99%

Untitled

Felty¹,

Roy²

2005

J Carcinog

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In this review, we discuss estrogen actions on mitochondrial function and the possible implications on cell growth. Mitochondria are important targets of estrogen action. Therefore, an in-depth analysis of interaction between estrogen and mitochondria; and mitochondrial signaling to nucleus are pertinent to the development of new therapy strategies for the treatment of estrogen-dependent diseases related to mitochondrial disorders, including cancer.

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NADH: Ubiquinone Oxidoreductase Inhibitors Block Induction of Ornithine Decarboxylase Activity in MCF‐7 Human Breast Cancer Cells*

Cited by 31 publications

References 24 publications

Mitochondrial Complex I Inhibitor Rotenone-Elicited Dopamine Redistribution from Vesicles to Cytosol in Human Dopaminergic SH-SY5Y Cells

Mitochondrial Complex I Inhibitor Rotenone-Elicited Dopamine Redistribution from Vesicles to Cytosol in Human Dopaminergic SH-SY5Y Cells

Mitochondria: A novel target for the chemoprevention of cancer

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