Role of ornithine decarboxylase in breast cancer

Deng, Wensheng; Jiang, Xian; Yu, Mingcan; Sun, Jingyu; Ma, Rong; Liu, Xianxi; Sun, Hui; Tian, Hui; Sun, Xueying

doi:10.1111/j.1745-7270.2008.00397.x

Cited by 32 publications

(20 citation statements)

References 23 publications

(16 reference statements)

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“…We also confirm the results of previous studies on SSAT and ODC enzyme activities carried out in human BC tissues compared with nonmalignant control, indicating a high ODC and SSAT activities in BC samples [12,38,39]. Manni et al [38] reported that increased ODC activity is associated with an increased risk of both disease recurrence and death, while Deng et al [39] showed that the overexpression of ODC in BC tissues correlates with the TNM grading system. Wallace et al [12] reported that the decrease of APAO activity in BC tissues positively correlated with the aggressiveness of the tumor, while the increase of SSAT activity showed a tendency to be indicative of a poor prognosis.…”

Section: Discussionsupporting

confidence: 91%

Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm

et al. 2010

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BackgroundPolyamine metabolism has a critical role in cell death and proliferation representing a potential target for intervention in breast cancer (BC). This study investigates the expression of spermine oxidase (SMO) and its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO enzyme.MethodsBC tissue samples were analyzed for SMO transcript level and SMO activity. Student's t test was applied to evaluate the significance of the differences in value observed in T and NT samples. The structure modeling analysis of BENSpm and CPENSpm complexes formed with the SMO enzyme and their inhibitory activity, assayed by in vitro experiments, were examined.ResultsBoth the expression level of SMO mRNA and SMO enzyme activity were significantly lower in BC samples compared to NT samples. The modeling of BENSpm and CPENSpm complexes formed with SMO and their inhibition properties showed that both were good inhibitors.ConclusionsThis study shows that underexpression of SMO is a negative marker in BC. The SMO induction is a remarkable chemotherapeutical target. The BENSpm and CPENSpm are efficient SMO inhibitors. The inhibition properties shown by these analogues could explain their poor positive outcomes in Phases I and II of clinical trials.

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Section: Discussionsupporting

confidence: 91%

Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm

et al. 2010

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“…These metabolites were also found to be significantly elevated in breast cancer tissue compared to normal tissue in a previous study that investigated a large cohort of breast cancer cases [8]. Via the action of ornithine decarboxylase (ODC), ornithine is the starting point for the synthesis of polyamines that are associated with tumor promotion and progression [18]. That study found that the level of ODC expression was highest in MDA-MB-231 cells, which implies that ornithine plays an important role in determining tumor growth and aggressiveness.…”

Section: Discussionmentioning

confidence: 99%

Comparative metabolic and lipidomic profiling of human breast cancer cells with different metastatic potentials

et al. 2016

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This study conducted comprehensive and comparative metabolic and lipidomic profiling of a human epithelial breast cell line (MCF-10A), a slightly metastatic (MCF-7), and a highly metastatic (MDA-MB-231) breast cancer cell line using gas chromatography mass spectrometry (GC-MS) and direct infusion mass spectrometry (DI-MS). Among 39 metabolites identified by GC-MS analysis, xanthine, glucose-6-phosphate, mannose-6-phosphate, guanine, and adenine were selected as prognostic markers of breast cancer metastasis. Major metabolic pathways involved in differentiation of the cell lines were alanine, aspartate, and glutamate metabolism, purine metabolism and glycine, serine, and threonine metabolism. Among 44 intact lipid species identified by DI-MS analysis, the levels of most phospholipids were higher in both metastatic groups than in normal cells. Specifically, the levels of phosphatidylserine (PS) 18:0/20:4, phosphatidylinositol (PI) 18:0/20:4, and phosphatidylcholine (PC) 18:0/20:4 were markedly higher while those of phosphatidylethanolamine (PE) 18:1/18:1 and PI 18:0/18:1 were lower in MDA-MB-231 cells than in MCF-7 cells. A partial-least-squares regression model was developed and validated for predicting the metastatic potential of breast cancer cells. The information obtained in this study will be useful when developing diagnostic tools and for identifying potential therapeutic targets for metastatic breast cancer.

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“…We found that NCAO had a highly potent antitumoral effect when tested in vitro against 13 tumor cell lines of diverse tissue origin (from humans and mice) and when tested in vivo in a mouse model using both solid and ascitic tumors. We selected cancer cell lines of various origins in which deregulation of cell proliferation was related to overexpression and high activity of ODC and that are representative of many cancers [10], such as MDA-MB-231 in breast cancer [22], HeLa in cervical cancer [23], and Raji in lymphoblastoma [24]. The NCAO exerted an in-vitro cytotoxic effect against cancer cell lines, irrespective of their origin, after 72 h of exposure.…”

Section: Discussionmentioning

confidence: 99%

N-ω-chloroacetyl-L-ornithine has in-vitro activity against cancer cell lines and in-vivo activity against ascitic and solid tumors

et al. 2016

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N-ω-chloroacetyl-L-ornithine (NCAO) is an ornithine decarboxylase (ODC) inhibitor that is known to exert cytotoxic and antiproliferative effects on three neoplastic human cancer cell lines (HeLa, MCF-7, and HepG2). Here, we show that NCAO has antiproliferative activity in 13 cancer cell lines, of diverse tissue origin from human and mice, and in a mouse cancer model in vivo. All cell lines were sensitive to NCAO after 72 h of treatment (the EC50 ranged from 1 to 50.6 µmol/l). The Ca Ski cell line was the most sensitive (EC50=1.18±0.07 µmol/l) and MDA-MB-231 was the least sensitive (EC50=50.6±0.3 µmol/l). This ODC inhibitor showed selectivity for cancer cells, exerting almost no cytotoxic effect on the normal Vero cell line (EC50>1000 µmol/l). NCAO induced apoptosis and inhibited tumor cell migration in vitro. Furthermore, in vivo, this compound (at 50 and 100 mg/kg, daily intraperitoneal injection for 7 days) exerted potent antitumor activity against both solid and ascitic tumors in a mouse model using the myeloma (Ag8) cell line. At these same two doses, the toxicological evaluation showed that NCAO has no obvious systemic toxicity. The current results suggest that the antitumor activity is exerted by apoptosis related not only to a local but also a systemic cytotoxic effect exerted by NCAO on tumor cells. The applications for NCAO as an antitumor agent may be extensive; however, further studies are needed to ascertain the antitumor activity on other types of tumor in vivo and to determine the precise molecular mechanism of its activity.

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Role of ornithine decarboxylase in breast cancer

Abstract: Role of ornithine decarboxylase in breast cancerActa Biochim Biophys Sin (2008): 235-243 |

Cited by 32 publications

References 23 publications

Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm

Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm

Comparative metabolic and lipidomic profiling of human breast cancer cells with different metastatic potentials

N-ω-chloroacetyl-L-ornithine has in-vitro activity against cancer cell lines and in-vivo activity against ascitic and solid tumors

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