5-FdUrd–araC heterodinucleoside re-establishes sensitivity in 5-FdUrd- and AraC-resistant MCF-7 breast cancer cells overexpressing ErbB2

Strasser, Stephen; Maier, Susanne; Leisser, Christina; Saiko, Philipp; Madlener, Sibylle; Bader, Yvonne; Bernhaus, Astrid; Gueorguieva, Marieta; Richter, Susanne; Mader, Robert M.; Węsierska‐Gądek, Józefa; Schott, Herbert; Szekeres, Thomas; Fritzer‐Szekeres, Monika; Krupitza, Georg

doi:10.1111/j.1432-0436.2006.00082.x

Cited by 20 publications

(17 citation statements)

References 26 publications

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“…Patients whose pathologic types, grades, and clinical stages are different have distinct risks for metastasis via blood vessels and therefore various prognoses. The other feature related to treatment failure is that some tumor cells are not sensitive to radiotherapy and chemotherapy; hence, they can survive and continue to grow and metastasize after treatment (18). At present, the pathologic method of diagnosing breast cancer is based on the morphology of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Identification of Metastasis-Related Proteins and Their Clinical Relevance to Triple-Negative Human Breast Cancer

Sun

Zhang

et al. 2008

Clinical Cancer Research

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Purpose: Currently, there are no definite biomarkers of triple-negative breast cancer. The study aims to identify the metastasis-associated proteins of triple-negative breast tumors. Experimental Design: A murine metastatic breast cancer model has been established by using TA2 mice. Parallel proteomic analyses were done on a murine metastatic breast cancer model and its primary breast cancer using two-dimensional gel electrophoresis. The differentially expressed proteins were detected inTA2 mice developing spontaneous breast cancer and lung metastasis. Furthermore, their expression were detected in human breast cancer with or without metastasis, and their prediction values were assessed in a second set of samples. Results: Nineteen of 36 differentially expressed proteins were identified by peptide mass fingerprinting using matrix-assisted laser-desorption ionization-time of flight-mass spectrometry.These proteins were also validated in mouse tumor tissues by immunohistochemical staining. Actin, 14-3-3, vimentin, HSP70, CK18, and moesin were up-regulated in the metastatic tumors, whereas HSP90 and tubulin were absent or down-regulated. Furthermore, 61patients with triple-negative breast cancer and 39 patients with estrogen receptor-positive/progesterone receptor-positive breast cancer were selected for exploring the clinical relevance of these identified proteins to human breast cancer metastasis. Expression of 14-3-3 and HSP70 was significantly correlated with metastasis of human triple-negative breast cancer. Moreover, the validation study in the second set confirmed that 14-3-3, HSP70, and their combination had high sensitivities and specificities in predicting metastatic potential of triple-negative breast cancer. Conclusions:These tumor metastasis-associated proteins validated may be useful as biomarkers and targets for diagnosis and treatment of human triple-negative breast cancer.Breast cancer metastasis is the main cause of treatment failure, exerting a remarkably negative effect on the cure and survival of patients suffering from breast cancer. Metastasis is a multiplestep process involving numerous genes (1, 2). There are two distinct hypotheses regarding tumor metastasis: heterogeneous metastasis and synchronous metastasis. Heterogeneous metastasis is defined as malignant tumor cells spreading to other organs in the late stage (3), whereas synchronous metastasis is described as tumor cells disseminating very early and evolving into metastatic disease independent from the primary tumor (4), suggesting that protein expression in the metastatic tumor may be different from the primary tumor (5). Therefore, the identification of metastasis protein markers in the early stage may contribute to early diagnosis and treatment of breast cancer patients with high risk of metastasis.Triple-negative breast cancer is the subtype of invasive breast cancer with estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER-2-negative phenotype, an important subtype of breast cancer due to its re...

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Section: Discussionmentioning

confidence: 99%

Identification of Metastasis-Related Proteins and Their Clinical Relevance to Triple-Negative Human Breast Cancer

Sun

Zhang

et al. 2008

Clinical Cancer Research

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“…The percent of cell divisions compared to the untreated control were calculated as follows: [(C 72h + drug -C 24h + drug )/ (C 72h -drug -C 24h -drug )] x 100 = % cell division, where C 72h + drug is the cell number after 72 h of extract treatment, C 24h + drug is the cell number after 24 h of extract treatment, C 72h -drug and C 24h -drug are the cell numbers after 72 and 24 h without extract treatment (18,19).…”

Section: Reagentsmentioning

confidence: 99%

Effects of Scrophularia extracts on tumor cell proliferation, death and intravasation through lymphoendothelial cell barriers

et al. 2012

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Abstract. Different studies describe the anti-inflammatory effects of Scrophularia species, a medicinal plant widely used in folk medicine since ancient times. As knowledge regarding the anti-neoplastic properties of this species is rather limited, we investigated the influence of methanol extracts of different Scrophularia species on cell proliferation, cell death, and tumour cell intravasation through the lymph endothelial barrier. HL-60 leukaemia cells were treated with methanol extracts of different Scrophularia species leading to strong growth inhibition and high cell death rates. The expression of cell cycle regulators, oncogenes and cell death inducers was determined by Western blot analysis. Furthermore the effect of S. lucida was studied in an NF-κB reporter assay, and in a novel assay measuring 'circular chemo-repellent-induced defects' (CCID) in lymph endothelial monolayers that were induced by MCF-7 breast cancer spheroids. Methanol extracts of Scrophularia species exhibited strong anti-proliferative properties. S. floribunda extract inhibited G2/M-and later on S-phase and S. lucida inhibited S-phase and in both cases this was associated with the down-regulation of c-Myc expression. Extracts of S. floribunda and S. lucida led to necrosis and apoptosis, respectively. Furthermore, S. lucida, but not S. floribunda, effectively attenuated tumour cell intravasation through lymph endothelial cell monolayers, which correlated with the inhibition of NF-κB. S. lucida exhibited promising anti-neoplastic effects and this was most likely due to the downregulation of various cell cycle regulators, proto-oncogenes and NF-κB and the activation of caspase-3.

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“…A major drawback of chemotherapeutic treatment in most cases is the development of resistances e.g. against AraC (32,33) and therefore, the chemotherapeutic armamentarium is limited and new concepts for adjuvant and second treatment options are needed. This justifies further investigations of this promising plant extract.…”

Section: Discussionmentioning

confidence: 99%

In vitro anti-neoplastic activity of the ethno-pharmaceutical plant Hypericum adenotrichum Spach endemic to Western Turkey

Özmen

Bauer²,

Gridling³

et al. 2009

Oncol Rep

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Abstract. Hypericum perforatum (St. John's wort) is wellestablished for its antidepressant activity throughout the world and also various other species within this genus are used in different folk medicines. Hyperforin of St. John's wort inhibited growth of cancer cell lines and the use of hypericin (another compound of H. perforatum) in cancer photodynamic therapy is proposed. Therefore, we investigated the anti-cancer properties of H. adenotrichum Spach (Guttiferae), an endemic species in Turkey called 'kantaron', which is used for wound healing and antiseptic effects. Freeze-dried plant was extracted with petroleum ether, dichloromethane, ethyl acetate, and methanol and the bioactivity of these extracts was analysed by proliferation assay, cell death determination, by investigating protein expression profiles specific for cell cycle arrest and apoptosis as well as composition by HPLC. The strongest anti-proliferative activity was determined for the petroleum ether extract with an I p C 50 of ~5.8 μg/ml medium (referring to 1 mg dried plant) which correlated with cyclin D1 suppression and p21 induction. This extract also induced phosphorylation of H2AX, and activated caspase-3 followed by signature-type cleavage of PARP resulting in ~50% apoptosis at 23.2 μg/ml after 24 h of treatment. Neither hyperforin, hypericin, or amentoflavone contributed to these properties. To the best of our knowledge, we report for the first time that the endemic plant H. adenotrichum Spach exhibits potent p53-independent anti-neoplastic properties due to yet unexplored Hypericum constituents. IntroductionSome 60% of all drugs used in Western medicine are derived from natural compounds which served as leads (1). From the 80's up to now pharmaceutical companies collect marine organisms, bacteria, fungi and plants at random to test them in robot-screenings regarding their anti-cancer, anti-inflammatory, anti-bacterial etc. activities. Another approach requests the ancient ethno-botanical knowledge of old civilizations which mostly base on the in depth and long lasting empirical experiences with the locally available natural resources, plants at most.Of the 12,000 plant species in Europe under consideration approximately 11,500 taxa are found in Turkey alone with 33% of these plants endemic. Since numerous ancient civilisations lived in the area, the plant societies were tested for medicinal applications throughout the ages and many plant species are still used in Turkish folk medicine to treat various diseases (2).The rich botanical biodiversity of this region paired with the cultural background was the reason to explore the traditional healing plant Hypericum adenotrichum, one of 43 Hypericum species endemic in Turkey. Within the genus Hypericum various species are used in different folk medicines worldwide and are tested against cancer cell growth.The genus Hypericum is called 'kantaron' in Turkey and H. adenotrichum is used in folk medicine for antispasmodic and antiseptic effects, and wound healing especially burns (2). The use of ...

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5-FdUrd–araC heterodinucleoside re-establishes sensitivity in 5-FdUrd- and AraC-resistant MCF-7 breast cancer cells overexpressing ErbB2

Cited by 20 publications

References 26 publications

Identification of Metastasis-Related Proteins and Their Clinical Relevance to Triple-Negative Human Breast Cancer

Identification of Metastasis-Related Proteins and Their Clinical Relevance to Triple-Negative Human Breast Cancer

Effects of Scrophularia extracts on tumor cell proliferation, death and intravasation through lymphoendothelial cell barriers

In vitro anti-neoplastic activity of the ethno-pharmaceutical plant Hypericum adenotrichum Spach endemic to Western Turkey

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