Cinnamolide sesquiterpene lactone suppresses in vitro and in vivo cancer cell growth in cisplatin-resistant human cervical carcinoma cells by inducing mitochondrial mediated apoptosis, caspase activation, loss of MMP and targeting Akt/ß-Catenin signaling pathway.

The Editors of JBUON issue an Expression of Concern to 'Cinnamolide sesquiterpene lactone suppresses in vitro and in vivo cancer cell growth in cisplatin-resistant human cervical carcinoma cells by inducing mitochondrial mediated apoptosis, caspase activation, loss of MMP and targeting Akt/ß-Catenin signaling pathway', by Jing Hou, Changli Kan, Yanju Zhu, Yi Zhang, Bingfeng Zhou, Chunli Ren, Jiuyuan Fu, Yanwei Guo, Jinhuan Zhang; JBUON 2020;25(2):709-715; PMID: 32521857. Following the publication of the above article, readers drew to our attention that part of the data was possibly unreliable. We sent emails to the authors with a request to provide the raw data to prove the originality, but received no reply. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

Cinnamolide sesquiterpene lactone suppresses in vitro and in vivo cancer cell growth in cisplatin-resistant human cervical carcinoma cells by inducing mitochondrial mediated apoptosis, caspase activation, loss of MMP and targeting Akt/ß-Catenin signaling pathway.

PURPOSE: This study was designed to examine the in vitro and in vivo antitumor effects of Cinnamolide against cisplatin-resistant human cervical cancer cells (HeLa cells). METHODS: Cell viability was examined by WST-1 cell viability assay. Cinnamolide-induced apoptosis was examined by fluorescent microscopy using acridine orange (ΑΟ) /ethidium bromide (EB) staining and flow cytometry in combination with annexin-V/propidium iodide (PI) staining. Western blot was used to study the effects of Cinnamolide on apoptosis-related protein expressions including Bax and Bcl-2 as well as to study effects on numerous caspases and Akt/ß-Catenin signaling pathway. Effects on mitochondrial membrane potential (MMP) were evaluated by flow cytometry. In vivo studies using xenograft mouse model were carried out to evaluate the efficacy of Cinnamolide under in vivo conditions. RESULTS: Cinnamolide decreased the viability of the HeLa human cervical cancer cells and exhibited an IC50 of 16.5 µM. The cytoxicity of Cinnamolide was also investigated on the MDCK normal cervical cells which showed that Cinnamolide exerted very low toxic effects on these cells. Cinnamolide also caused remarkable changes in the morphology of the HeLa cancer cells and suppressed their colony forming potential. The AO/EB staining showed that this molecule inhibits the viability of cancer cells via induction of apoptotic cell death which was associated with increase in Bax and decrease in Bcl-2 levels. The apoptotic cells increased from 3.5% in control to around 59% in HeLa cells at 50 µM concentration. Cinnamolide treatment also led to activation of caspase-3 and caspase-9. It was also seen that Cinnamolide treatment led to a significant and dose-dependent loss of MMP in HeLa cancer cells. It also significantly inhibited the Akt/ß-catenin signalling pathway by reducing the levels of phosphorylated Akt and GSK-3ß. The results also showed that Cinnamolide suppressed the tumor volume and the tumor weight of the xenografted tumors. CONCLUSION: The results of this study indicate that Cinnamolide natural product has the potential to be developed as a promising anticancer agent against human cervical carcinoma.

Correlation of miR-21 and BNP with pregnancy-induced hypertension complicated with heart failure and the diagnostic value.

Correlation of miR-21 and B-type natriuretic peptide (BNP) with pregnancy-induced hypertension (PIH) complicated with heart failure and the diagnostic value was investigated. Sixty patients with PIH complicated with heart failure admitted to Affiliated Hospital of Chengde Medical University from July 2016 to July 2017 were enrolled as the experimental group, and 35 normal pregnant women as the control group. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) method was used to determine the expression level of plasma miR-21 expression level. An automatic biochemical analyzer was used to determine plasma BNP expression level. Spearmans correlation analysis was used for the correlation analysis of miR-21 and BNP. ROC curve was used for evaluating the diagnostic values of miR-21 and BNP for PIH complicated with heart failure. miR-21 and BNP expression levels were higher in patients with PIH complicated with heart failure than those in the normal individuals, and were increased in line with the heart failure grade (P<0.001). The plasma miR-21 expression was positively correlated with BNP in patients with PIH complicated with heart failure (r=0.685, P<0.001). Both miR-21 and BNP had higher diagnostic values for PIH complicated with heart failure, in the diagnosis, the best cut-off value [odds ratio (OR)] of miR-21 was 1.113, with an area under curve (AUC) of 0.889 and a 95% confidence interval (CI) of 82.05-95.76%; the OR of BNP was 123, with an AUC of 0.747 and a 95% CI of 64.95-84.38%. Blood pressure, six-minute walk test (6MWT), left ventricular ejection fraction (LVEF) and left ventricular end diastolic diameter (LVEDD) were independent risk factors for the occurrence of PIH complicated with heart failure (P<0.05). In conclusion, miR-21 and BNP, highly expressed in patients with PIH complicated with heart failure, are expected to become important biomarkers for diagnosing PIH complicated with heart failure and judging the degree of heart failure in the patients, and worthy of clinical popularization and application.