Downregulation of ornithine decarboxylase by pcDNA-ODCr inhibits gastric cancer cell growth in vitro

Xu, Chunxiao; Yan, Yun‐Fei; Yang, Yong; Liu, Bin; Xin, Jiaxuan; Chen, Shimin; Wang, Wei; Jiang, Chunying; Lu, Zhaoxin; Liu, Xianxi

doi:10.1007/s11033-010-0188-x

Cited by 10 publications

(2 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conversely, there is convincing evidence that a low level of ODC activity reduces carcinogenesis [34]. There are few reports of utilizing RNAi to downregulate ODC in various cancers [35,36].…”

Section: Discussionmentioning

confidence: 99%

Targeting polyamine biosynthetic pathway through RNAi causes the abrogation of MCF 7 breast cancer cell line

et al. 2015

View full text Add to dashboard Cite

The diamine putrescine and polyamines, spermidine (triamine) and spermine (tetraamine) are small organic polycations that play an indispensable role in key cellular processes such as the regulation of growth, differentiation, and macromolecular functions. Elevated levels of polyamines (PAs) have been shown to be one of the major factors involved in carcinogenesis. In this study, specific silencing of the expression of three genes of PA biosynthesis pathway, ornithine decarboxylase (ODC), S-adenosylmethionine decarboxylase (SAMDC), and spermidine synthase (SPDSYN) was achieved using RNA interference in MCF 7 breast cancer cell line. For optimizing the effective small interfering nucleic acid (siNA), three variants of ODC siNA [siRNA, locked nucleic acid (LNA)-modified siRNA, and siHybrid (RNA and DNA hybrid)] were used and a dose- and time-dependent study was conducted. The PA biosynthetic genes were targeted individually and in combination. RNAi-mediated reduction in the expression of PA biosynthesis genes resulted in distorted cell morphology, reduced cancer cell viability, and migration characteristic. The most promising results were observed with the combined treatment of siSPDSYN and siODC with 83 % cell growth inhibition. On analyzing the messenger RNA (mRNA) expression profile of the cell cycle and apoptosis-related genes, it was observed that RNAi against PA biosynthetic genes downregulated the expression of CDK8, CCNE2, CCNH, CCNT1, CCNT2, CCNF, PCNA, CCND1, and CDK2, and upregulated the expression of E2F4, BAX, FAS, TP53, CDKN1A, BAK1, CDKN1B, ATM, GRANB, and ATR genes when compared with control-transfected cells. These results suggest that the targeting polyamine biosynthesis through RNAi approach could be a promising strategy for breast cancer therapy and might be extended for therapy of other cancers.

show abstract

Section: Discussionmentioning

confidence: 99%

Targeting polyamine biosynthetic pathway through RNAi causes the abrogation of MCF 7 breast cancer cell line

et al. 2015

View full text Add to dashboard Cite

show abstract

“…The molecular dysregulation of the ODC1 gene could alter its expression patterns and leads to overexpression in cancer cells. Studies have revealed that ODC downregulation and activity decline could be associated with the reduced growth of cancer cells (6,7). The current chemical drugs against cancer cells are primarily ineffective and associated with several unwanted side effects.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic Effects of Rheum khorasanicum Extract on MCF-7 Human Breast Cancer Cell Line and ODC1 Gene Expression

Noori

Afshar

2022

Jentashapir J Cell Mol Biol

View full text Add to dashboard Cite

Background: Polyamine metabolism has a critical role in cancer initiation and progression. The abnormal overexpression of the ornithine decarboxylase (ODC1) enzyme gene could be a characteristic of cancer cells. Objectives: The current study evaluated the cytotoxic effects of Rheum khorasanicum extract in three different solvents, including distilled water, ethanol, and n-hexane, on the MCF-7 breast cancer cell line and assessed the expression level of the ODC1 gene upon the abovementioned treatments. Methods: We cultured MCF-7 cancer cells in complete cell culture media and subsequently subjected them to increasing concentrations (0 - 200 μg/mL) of the extract. The cytotoxic activity of the extract was investigated using an MTT assay. The quantitative analysis of ODC1 gene expression was performed using real-time PCR. Results: The cell viability was significantly decreased in concentration- and time-dependent manners. The mRNA expression of the ODC1 gene declined gradually with the increasing concentrations of extracts. Conclusions: Our findings indicated that R. khorasanicum extract could potentially influence ODC1 gene expression in breast cancer cells and exert inhibitory effects on cancer cell proliferation.

show abstract

A new 68Ga-labeled ornithine derivative for PET imaging of ornithine metabolism in tumors

et al. 2023

View full text Add to dashboard Cite

Ornithine metabolism plays a vital role in tumorigenesis. For cancer cells, ornithine is mainly used as a substrate for ornithine decarboxylase (ODC) to produce amounts of polyamines. The ODC as a key enzyme of polyamine metabolism has become an important target for cancer diagnosis and treatment. To non-invasively detect the levels of ODC expression in malignant tumors, we have synthesized a novel 68 Ga-labeled ornithine analog ( 68 Ga-NOTA-Orn). The synthesis time of 68 Ga-NOTA-Orn was about 30 min with a radiochemical yield of 45-50% (uncorrected), and the radiochemical purity was > 98%. 68 Ga-NOTA-Orn was stable in saline and rat serum. Cellular uptake and competitive inhibition assays using DU145 and AR42J cells demonstrated that the transport pathway of 68 Ga-NOTA-Orn was similar to that of Lornithine, and it could interact with the ODC after transporting into the cell. Biodistribution and micropositron emission tomography (Micro-PET) imaging studies showed that 68 Ga-NOTA-Orn exhibited rapid tumor uptake and was rapidly excreted through the urinary system. All above results suggested that 68 Ga-NOTA-Orn is a novel amino acid metabolic imaging agent with great potential of tumor diagnosis.

show abstract

Downregulation of ornithine decarboxylase by pcDNA-ODCr inhibits gastric cancer cell growth in vitro

Cited by 10 publications

References 37 publications

Targeting polyamine biosynthetic pathway through RNAi causes the abrogation of MCF 7 breast cancer cell line

Targeting polyamine biosynthetic pathway through RNAi causes the abrogation of MCF 7 breast cancer cell line

Cytotoxic Effects of Rheum khorasanicum Extract on MCF-7 Human Breast Cancer Cell Line and ODC1 Gene Expression

A new 68Ga-labeled ornithine derivative for PET imaging of ornithine metabolism in tumors

Contact Info

Product

Resources

About