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.

Astaxanthin inhibiting oxidative stress damage of placental trophoblast cells in vitro.

Oxidative stress from the trophoblasts is one of the possible pathological mechanisms of Preeclampsia (PE). This study aimed at exploring the potential effects of astaxanthin (ATX) on oxidative stress damaged placental trophoblast cell line HTR-8/SVneo. Oxidative stress-induced damaged through H2O2 treatment was checked by MTS CellTiter 96® cell viability, 2',7'-dichlorofluorescein diacetate (DCFH-DA) induced fluorescence, the level of the intracellular malondialdehyde (MDA), and the detection of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT). Different concentrations of ATX were applied, and then the proliferation rate, apoptotic percentage, cell cycle distribution, invasion test and relative biological function of the rescued cells were followed. We provide evidence that ATX had an anti-oxidative effect against oxidative stress induced by H2O2 on the trophoblast cell line and had beneficial role in promoting cell proliferation, inhibiting cell apoptosis, and inducing cell invasion.Abbreviations: UV: ultraviolet; DCFH-DA: 2',7'-dichlorofluorescein diacetate; EVT: extravillous trophoblast; MMPs: matrix metalloproteinases; IUGR: intrauterine growth restriction.

Neutrophil extracellular trap from Kawasaki disease alter the biologic responses of PBMC.

Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome, is an acute systemic vasculitis syndrome that mainly occurs in infants under 5 years of age. In the current manuscript, we were aiming to analyze the role of neutrophil extracellular traps (NETs) in the pathogenesis of KD, especially their interplay with peripheral blood mononuclear cells (PBMCs). Neutrophils were exposed to 20 nM phorbol myristate acetate (PMA), we found that neutrophils of KD patients were more likely to form NETs compared with healthy controls (HCs). Furthermore, PBMCs were cultured with NETs for 24 h, and we observed that NETs significantly increased the cell viability, suppressed cell apoptosis, and enhanced the pro-inflammatory cytokines production and NF-κB activation in PBMCs from KD patients. In addition, with the stimulation of NETs, the expression of vascular endothelial growth factor A (VEGF-A) and hypoxia-inducible factor-1α (HIF-1α) were increased, which were related with the pathological mechanism of KD. At last, we examined the activation of phosphoinositide 3 kinase (PI3K)/Akt signaling, and we found NETs treatment obviously enhanced the activation of PI3K and Akt. In conclusion, these findings suggested that the formation of NETs may alter the biologic responses of PBMC and affect the vascular injury in KD.

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.