EF24 Induces G2/M Arrest and Apoptosis in Cisplatin-resistant Human Ovarian Cancer Cells by Increasing PTEN Expression

Selvendiran, Karuppaiyah; Tong, Liyue; Vishwanath, Shilpa; Bratasz, Anna; Trigg, Nancy J.; Kutala, Vijay Kumar; Hideg, Kálmán; Kuppusamy, Periannan

doi:10.1074/jbc.m703796200

Cited by 124 publications

(151 citation statements)

References 44 publications

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“…However, the treatment can still be viewed largely as a 'shot in the dark' and the tools available to help predict who will respond optimally to which treatment are still relatively crude. Some molecules, such as BRCA1 (Quinn et al, 2007), soluble Fas levels (Chaudhry et al, 2008), Death Receptor 4 and TNF receptor 2 (TNFR2) (Dong et al, 2008), EF24 (Selvendiran et al, 2007), and trophinin (Baba et al, 2007), have been shown to correlate with cisplatin resistance in human ovarian cancer. The molecular markers involved in the activity of chemotherapeutic agents can shed light on the successes and failures of treatment in ovarian cancer patients and can also provide a basis for individualised therapy.…”

Section: Discussionmentioning

confidence: 99%

High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma

et al. 2009

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The objective of this paper is to investigate the mesothelin expression level to the clinicopathological features, chemoresponse, and to the outcome of patients with epithelial ovarian carcinoma (EOC). Mesothelin mRNA was detected by real-time quantitative reverse-transcription PCR in 139 EOC patients. Clinical characteristics, histopathological items, responses to chemotherapy, progression-free survival (PFS), and overall survival (OS) were recorded. Tumours with advanced stages had higher mesothelin than those with early stages. The chemoresistant patients showed significantly higher mesothelin than did chemosensitive patients (2.81 vs 0.43, Po0.001), irrespective of optimal or suboptimal surgery in those with advanced stages. Highly expressed levels of mesothelin were an independent but poor prognostic factor in the PFS (2.03 (1.23 -3.37) P ¼ 0.006) and ), P ¼ 0.002) of the 139 EOC patients in multivariate analysis. In addition, patients in advanced stages with highly expressed mesothelin also had significantly worse OS, regardless of whether they had undergone optimal (13.85 (1.76 -125.60), P ¼ 0.013) or suboptimal (4.47 (1.83 -10.88), P ¼ 0.001) debulking surgery in multivariate analysis. Out results provide new evidence that mesothelin expression is associated with chemoresistance and with shorter disease-free survival and worse OS of patients with EOC.

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Section: Discussionmentioning

confidence: 99%

High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma

et al. 2009

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“…PTEN encodes a multifunctional protein with a protein and lipid phosphatase activities, which interferes with the PI3K/AKT signal transduction, causing a blockade in the G phase of the cell cycle (28). Furthermore, PTEN has been demonstrated to negatively regulate the PI3K/AKT pathway, as well as induce cell apoptosis and proliferation (29)(30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-30a-3p overexpression improves sepsis-induced cell apoptosis inï¿½vitro and inï¿½vivo via the PTEN/PI3K/AKT signaling pathway

et al. 2017

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Abstract. The aim of the present study was to explain the mechanism of miR-30a-3p overexpression in sepsis-induced cell apoptosis in vitro and in vivo. For the in vitro cell experiments, H9c2 cells were divided into three groups, including the untreated normal control (NC), lipopolysaccharide (LPS)-treated and miRNA (treated with LPS and transfection with miRNA-30a-3p) groups. The cell proliferation and apoptosis were evaluated by MTT assay and flow cytometry, respectively. The relative protein expression levels were measured by western blot assay. In the in vivo experiment, a sepsis rat model was established by intraperitoneal injection of LPS. Sprague Dawley rats were divided into three groups, including the NC, LPS-injected and miRNA (in which model rats were injected with miR-30a-3p vector at the caudal vein) groups. The myocardial morphology in different groups was observed by hematoxylin and eosin staining. In addition, tissue apoptosis and protein expression levels were evaluated by TUNEL and western blot assay, respectively. The results of cell experiments indicated that the cell proliferation rate was significantly increased and the cell apoptosis rate was significantly downregulated in the miR-30a-3p group compared with the LPS group (both P<0.05). The relative protein expression of phosphatase and tensin homolog (PTEN) was markedly decreased in the miRNA group compared with the LPS group, while the levels of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) were significantly increased in the miRNA group (all P<0.05). In the in vivo experiments, the myocardial morphology of the miRNA group was improved compared with that of the LPS group. Compared with the LPS group, cell apoptosis in the miRNA group was significantly downregulated (P<0.05), while the relative protein levels (PTEN, PI3K and AKT) in the tissues were also significantly altered (P<0.05). In conclusion, miR-30a-3p overexpression may improve the sepsis-induced cell apoptosis in vitro and in vivo via the PTEN/PI3K/AKT signaling pathway.

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“…The literature refers to this pharmacophore as a curcumin analogue [5], and a substantial number of these compounds have excellent antineoplastic properties [2,[6][7][8][9][10]. Other laboratories are also examining the biological potential of this pharmacophore [5,[11][12][13]. In order to initiate some in vitro and in vivo studies on a rational basis, a robust analytical method is mandatory.…”

Section: Introductionmentioning

confidence: 99%

A general HPLC–UV method for the quantitative determination of curcumin analogues containing the 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore in rat biomatrices

Singh

Das

Dimmock

et al. 2010

Journal of Chromatography B

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Curcumin and its derivatives generally display favorable cytotoxic activities against a number of cancer cell types. We focus our rational antineoplastic drug design program on curcumin analogues containing the 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore. Favorable outcomes from pharmacological screens of this series demanded further pharmacokinetic evaluations to determine their suitability as effective compounds in vivo. To allow such evaluations and to provide a general, sensitive, rapid and simple method for the analysis of compounds containing the 1,5-diaryl-3-oxo-pentadienyl scaffold, we developed an HPLC method with ultraviolet detection for their detection in various biological matrices of a relevant preclinical species, i.e. the rat. Our HPLC method is specific for the analysis of many members in this series in rat blood, plasma, serum and hepatic microsomes following liquid-liquid extraction with TBME (1:30, v/v). The assay procedure involves chromatographic separation on a Zorbax-Eclipse C-18 column under isocratic conditions with the mobile phase consisting of acetonitrile and ammonium acetate buffer (pH 5.0, 10 mM) in different ratios depending upon the compound. The method was validated for NC 2083 in rat serum and rat liver microsomes, a potential lead compound, to demonstrate its applicability. The standard curve was linear (r 2 ≥ 0.997) from 50 to 5000 ng/mL. Intra-and interday precision and accuracy of the method were within USFDA specified limits. The stability of NC 2083 was established in an auto-injector, on bench-top, during freeze-thaw cycles and longterm stability at −80 °C for 40 days. The method is suitable for a number of compounds containing the 1,5-diaryl-3-oxo-pentadienyl scaffold with divergent log P values with only minor adjustments in the buffer to acetonitrile ratio of the mobile phase.

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EF24 Induces G2/M Arrest and Apoptosis in Cisplatin-resistant Human Ovarian Cancer Cells by Increasing PTEN Expression

Cited by 124 publications

References 44 publications

High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma

High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma

MicroRNA-30a-3p overexpression improves sepsis-induced cell apoptosis inï¿½vitro and inï¿½vivo via the PTEN/PI3K/AKT signaling pathway

A general HPLC–UV method for the quantitative determination of curcumin analogues containing the 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore in rat biomatrices

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