[Retracted] In vitro and in vivo anticancer effects of marmesin in U937 human leukemia cells are mediated via mitochondrial­mediated apoptosis, cell cycle arrest, and inhibition of cancer cell migration.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that a pair of tumors in Fig. 10 appeared to have been duplicated, although one of the tumors appeared at a larger size in the figure relative to the first one. Furthermore, the flow cytometric plots shown in Fig. 2B in the above paper appeared to be remarkably similar to data presented in a paper published in Phytomedicine [Sui C­G, Meng F­D and Jiang Y­H: Antiproliferative activity of rosamultic acid is associated with induction of apoptosis, cell cycle arrest, inhibition of cell migration and caspase activation in human gastric cancer (SGC­7901) cells. Phyomedicine 22: 796­806, 2015]. After having conducted an independent investigation in the Editorial Office, the Editor of Oncology Reports has determined that the above paper should be retracted from the Journal on account of a lack of confidence concerning the originality and the authenticity of the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office never received any reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. [the original article was published in Oncology Reports 39: 597­602, 2018; DOI: 10.3892/or.2017.6147].

In vitro and in vivo anticancer effects of marmesin in U937 human leukemia cells are mediated via mitochondrial-mediated apoptosis, cell cycle arrest, and inhibition of cancer cell migration.

Leukemia is one of the highly lethal cancers among all pediatric cancers. With limited drug options and the severe side effects associated with the current chemotherapy, there is pressing need to look for new and novel anticancer agents. Against this backdrop, in the present study we evaluated the anticancer activity of a natural coumarin, marmesin against human leukemia cell line U937 and normal human monocytes It was observed that marmesin exhibited an IC50 value of 40 µM and exerted its cytotoxic effects in a dose-dependent manner. However, the cytotoxic effects of marmesin were comparatively lower for the normal human monocytes as evident from the IC50 of 125 µM. Our results indicated that marmesin inhibits colony formation and induces apoptosis dose-dependently. We also investigated the effect of marmesin on the expression of Bax and Bcl-2 proteins. It was observed that marmesin treatment triggered upregulation of Bax and downregulation of Bcl-2 causing significant increase in the Bax/Bcl-2 ratio, marmesin could also induce ROS mediated alterations in mitochondrial membrane potential. Additionally, marmesin induced G2/M cell cycle arrest and significantly inhibited cell migration potential of leukemia cells at the IC50. Remarkably, marmesin prevent tumor growth significantly in vivo at the dosage of 30 mg/kg in vivo. These results strongly indicate that marmesin may prove to be a novel anticancer lead for the management of leukemia.

Exendin-4 alleviates high glucose-induced rat mesangial cell dysfunction through the AMPK pathway.

BACKGROUND/AIMS: Glucagon-like peptide-1 (GLP-1), which counteracts insulin resistance in humans with type 2 diabetes, has been shown to ameliorate diabetic nephropathy in experimental models. However, the mechanisms through which GLP-1 modulates renal function remained illdefined. The present study investigated the putative mechanisms underlying effects of exendin-4, a GLP-1 analog, on mesangial cell proliferation and fibronectin. METHODS: Rat mesangial cells (MCs) were treated with exendin-4 under high glucose conditions. AMP-activated protein kinase (AMPK) inhibitors (compound C) and agonists (AICAR) were used to analyze the role of this kinase. Cell proliferation was measured using a MTT assay. Fibronectin expression and AMPK-signaling pathway activity were assessed using ELISA and Western blotting, respectively. The production of matrix metalloproteinase (MMP)-2 and tissue inhibitors of metalloproteinases (TIMP)-2 was evaluated using quantitative real-time RT-PCR. RESULTS: Exendin-4 inhibited cell proliferation and fibronectin secretion in high glucose-induced MCs. It also caused phosphorylation of AMPK and subsequently increased the ratio of MMP-2 to TIMP-2, which resulted in the degradation of fibronectin. Exendin-4 reversed extracellular signal-regulated kinase (ERK) phosphorylation and enhanced expression of mammalian target of rapamycin (mTOR) in MCs. Moreover, the activation of the AMPK pathway by exendin-4 was induced by AICAR, which was inhibited by compound C. CONCLUSION: Exendin-4 exerts an inhibitory effect on cell proliferation and fibronectin secretion in rat MCs, partly through AMPK activation. These results may explain some of the beneficial effects of exendin-4 on the kidney.

[Study of WIF-1 promoter methylation with expressions of ß-catenin in acute leukemia].

OBJECTIVE: To explore the significance of WIF-1 gene promoter methylation and the expression of ß-catenin in acute leukemia (AL) patients. METHODS: The method of methylation specific polymerase chain reaction was employed to detect the status of WIF-1 gene methylation in 55 acute leukemia patients and normal controls from January 2009 to June 2010 in our hospital. The expression of ß-catenin was measured by flow cytometry. RESULTS: The methylation of WIF-1 gene promoter was found in 32.7% (18/55) AL patients. And the percentage was significantly higher than that of the controls (0). The patients with the methylation of WIF-1 gene had a lower complete remission rate (38.9%, 7/18) for the first chemotherapy than those without (81.1%, 30/37) (P < 0.05). The expressions of ß-catenin in methylation AL patients and those with non-methylation were 17.5% ± 3.3% and 15.4% ± 3.6% respectively. And they were significantly higher than the controls (10.5% ± 1.5%, P < 0.05). The expression of ß-catenin was higher in positive methylation patients than those negative ones (P < 0.05). CONCLUSION: The methylation of WIF-1 gene promoter and ß-catenin may be involved in the abnormal activation of Wnt/ß-catenin signal in acute leukemia.

[A preliminary study on the implication of Apaf-1 promoter methylation and the expression of apoptosis inhibitor protein Apollon in adult acute leukemia].

OBJECTIVE: To investigate the role of Apaf-1 gene promoter methylation and apoptosis inhibitor protein Apollon in pathogenesis of acute leukemia (AL) and their clinical significance. METHODS: Methylation specific PCR (MSP) was used to detect the methylation status of Apaf-1 gene promoter in 53 AL patients (28 AML, 10 ALL and 15 relapsed) and 10 healthy or nonmalignant blood diseases patients as control. RT-PCR was used to detect the expression levels of Apaf-1 mRNA and immunocytochemistry to detect the expression levels of Apollon protein. RESULTS: The abnromal methylation of Apaf-1 gene promotor in AL was 18/53(33.9%). No Apaf-1 mRNA was detected in methylation positive patients. Only one case in healthy and nonmalignant individuals was deletion of Apaf-1 mRNA expression without abnormal methylation. The positive methylation rate in AL bone marrow mononuclear cells was significantly higher than that in controls (P < 0.05). The expressin levels of Apollon protein in AL patients was higher than that in control (P < 0.05). The positive methylation ratio and Apollon protein level were higher in white blood cell count > 10 × 10(9)/L than in ≤ 10 × 10(9)/L (P < 0.05). There is a positive correlaiton between positive methylation ratio and Apollon protein expression in AL patients. CONCLUSION: Abnormal methylation of Apaf-1 gene promotor and high expression of Apollon might involved in leukemogenesis.