p21Cip/WAF1 activation is an important factor for the ERK pathway dependent anti-proliferation of colorectal cancer cells

Park, Ki‐Sook; Jeon, Soung Hoo; Oh, Jisun; Choi, Kang Yell

doi:10.1038/emm.2004.71

Cited by 19 publications

(21 citation statements)

References 24 publications

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“…S. floribunda clearly increased the p21 level after 4 h, while S. lucida extract inhibited p21 expression within 4 h. Although p21 is a prominent transcriptional target of p53 another pathway must have triggered the p21 increase since HL-60 cells are p53-deficient (25). As also the activation of the MEK-Erk pathway was shown to up-regulate p21 (26,27), we checked the phosphorylation status of Erk1/2. S. floribunda showed a slight increase of the phosphorylation status of Erk1/2 at the 4-h time-point going along with the p21 up-regulation.…”

Section: Anti-proliferative Activitymentioning

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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Section: Anti-proliferative Activitymentioning

confidence: 99%

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

et al. 2012

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“…Although HL-60 cells are p53 deficient (19), Western blot analysis showed an up-regulation of p21 until 4 h upon treatment with A. schlechtendalii root extract, and thereafter a return to control levels. Besides p53, also MEK-Erk1/2 were shown to up-regulate p21 (20,21) and this could have been achieved by the observed activation of Erk1/2 within 30 min of treatment.…”

Section: Discussionmentioning

confidence: 97%

A polar extract of the Maya healing plant Anthurium schlechtendalii (Aracea) exhibits strong in vitro anticancer activity

Stark

Gridling²,

Madlener³

et al. 2009

Int J Mol Med

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Abstract. The Aracea Anthurium schlechtendalii and Syngonium podophyllum are traditional remedies for the treatment of severe and chronic inflammatory conditions. We cross-examined these plants regarding their anti-neoplastic properties, because several anti-inflammatory molecular targets are common for both pathologic conditions due to similar signalling pathways. Two malignant cell lines, HL-60 and MCF-7, were treated with increasing concentrations of plant extracts of increasing polarity. The potential of the extracts to inhibit the cell cycle and to induce cell death was investigated, because these are relevant endpoints to assess the anti-cancer potential in vitro and the protein expression and cell cycle distribution upon exposure to the strongest extract was analysed. Extracts from S. podophyllum were rather ineffective, but the freeze-dried (but not air-dried) roots of A. schlechtendalii exhibited strong growth inhibitory and apoptosis-inducing properties. In HL-60 cells 50% proliferation inhibition was achieved by 1.7 μg dichloromethane extract/ml medium and correlated with the activation of Chk2, down-regulation of Cdc25A, suppression of cyclin D1 level, and transient induction of p21. This extract efficiently triggered apoptosis, which was confirmed by caspase 3 activation. The polymerisation of ·-tubulin and its subsequent degradation that depleted the cells from the G2/M contributed to apoptosis induction, because proper spindleformation during mitosis is mandatory for survival. In conclusion, we demonstrated that A. schlechtendalii root extract specifically targeted carcinogenic mechanisms, because Cdc25A and cyclin D1 are oncogenes that are frequently overexpressed in a variety of cancer entities and further, this extract affected microtubule function reminiscent of taxol.

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“…The major regulator of the p21 tumour suppressor protein is p53, but also Erk was reported to induce p21 (24,25) and here it was demonstrated that the PE extract activated Erk in p53-deficient HL-60 cells (23); ii) the downregulation of cyclin D1 and hence, the inhibition of Cdk4 and/or Cdk6 (28)(29)(30). Cyclin D1 is an oncogene that is overexpressed in various cancer types (31) and therefore, cyclin D1 is a target for anti-neoplastic therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Since HL-60 cells are p53 deficient (23), the upregulation of p21, which is a prominent transcriptional target of p53, must have been triggered by another pathway. Besides p53, also the activation of the MEK-Erk pathway was shown to upregulate p21 (24,25). Therefore, MEK-Erk signalling was investigated utilising phospho-specific antibodies.…”

Section: Anti-proliferative Activity Of the Extracts Of H Adenotrichummentioning

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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p21Cip/WAF1 activation is an important factor for the ERK pathway dependent anti-proliferation of colorectal cancer cells

Cited by 19 publications

References 24 publications

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

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

A polar extract of the Maya healing plant Anthurium schlechtendalii (Aracea) exhibits strong in vitro anticancer activity

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

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