α-Terthienylmethanol, isolated from Eclipta prostrata, induces apoptosis by generating reactive oxygen species via NADPH oxidase in human endometrial cancer cells

Lee, Jae Seung; Ahn, Ji-Hye; Cho, Yoon-Jin; Kim, Hayeong; Yang, Yeong-In; Lee, Kyung‐Tae; Jang, Dae Sik; Choi, Jung‐Hye

doi:10.1016/j.jep.2015.04.029

Cited by 28 publications

(16 citation statements)

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“…Values are mean ± SD of six mice per HRW group and three mice per NC group (See Additional file 11) It is extremely important to find efficient and safe clinical applications for activating pyroptosis in endometrial cancer. Since ROS constitutes an upstream mechanism implicated in cellular pyroptosis, and because ROS concentrations are higher in endometrial cancer than in normal endometrial tissue, we hypothesize that elevated ROS will lead to activation of cell death by pyroptosis in endometrial cancer cells [44][45][46]. Investigators have increasingly accepted either H 2 gas or H 2 -rich saline as promising candidates in therapeutic approaches to cancer [23].…”

Section: Discussionmentioning

confidence: 99%

Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway

et al. 2020

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Background: Pyroptosis belongs to a novel inflammatory programmed cell death pathway, with the possible prognosis of endometrial cancer related to the terminal protein GSDMD. Hydrogen exerts a biphasic effect on cancer by promoting tumor cell death and protecting normal cells, which might initiate GSDMD pathway-mediated pyroptosis. Methods: We performed immunohistochemical staining and western immunoblotting analysis to observe expression of NLRP3, caspase-1, and GSDMD in human and xenograft mice endometrial cancer tissue and cell lines. We investigated treatment with hydrogen could boost ROS accumulation in endometrial cancer cells by intracellular and mitochondrial sources. GSDMD shRNA lentivirus was used to transfect endometrial cancer cells to investigate the function of GSDMD protein in pyroptosis. Propidium iodide (PI) staining, TUNEL assay, measurement of lactate dehydrogenase (LDH) release and IL-1β ELISA were used to analysis pyroptosis between hydrogensupplemented or normal culture medium. We conducted in vivo human endometrial tumor xenograft mice model to observe anti-tumor effect in hydrogen supplementation. Results: We observed overexpression of NLRP3, caspase-1, and GSDMD in human endometrial cancer and cell lines by IHC and western immunoblotting. Hydrogen pretreatment upregulated ROS and the expression of pyroptosisrelated proteins, and increased the number of PI-and TUNEL-positive cells, as well as the release of LDH and IL-1β, however, GSDMD depletion reduced their release. We further demonstrated that hydrogen supplementation in mice was sufficient for the anti-tumor effect to inhibit xenograft volume and weight of endometrial tumors, as mice subjected to hydrogen-rich water displayed decreased radiance. Tumor tissue sections in the HRW groups presented moderate-to-strong positive expression of NLRP3, caspase-1 and GSDMD. Hydrogen attenuated tumor volume and weight in a xenograft mouse model though the pyroptotic pathway. Conclusions: This study extended our original analysis of the ability of hydrogen to stimulate NLRP3 inflammasome/GSDMD activation in pyroptosis and revealed possible mechanism (s) for improvement of antitumor effects in the clinical management of endometrial cancer.

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Section: Discussionmentioning

confidence: 99%

Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway

et al. 2020

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“…Consistent with these observations, an increase in cell number in subG1 in vitro and the intratumoral increase of caspase-3 in vivo after treatment with the complex nutrient mixture points to the induction of programmed cell death within tumor foci by this compound. The hypoxic and inflammatory tumor microenvironment induces the activation of anti-apoptotic pathways supporting the effect of anti-inflammatory or anti-oxidative drugs which have been shown to increase the sensitivity of tumor cells to pro-apoptotic signals ( 25 ). In addition to its effects in tumor cell proliferation and apoptosis, OOS reduced the migratory potential of C26 colon carcinoma cells in vitro .…”

Section: Discussionmentioning

confidence: 99%

Ocoxin® oral solution slows down tumor growth in an experimental model of colorectal cancer metastasis to the liver in Balb/c mice

et al. 2015

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Liver metastatic disease is the main cause of death in colorectal cancer (CRC) patients. During metastatic spread of the disease an imbalance in the oxidative stress and inflammation plays a crucial role in tumor progression. In order to improve the efficacy of current therapies, new complementary therapeutic approaches are being analyzed including biologically active compounds with low side effects. The anti-inflammatory and anti-oxidant properties of Ocoxin® oral solution (OOS) prompt us to analyze its effect on the metastatic development of CRC to the liver. First, in vitro effect of OOS in tumor cell viability and migration was analyzed. Second, in vivo effect of different dosage patterns and concentrations in the development of hepatic metastasis was analyzed by intrasplenic inoculation of C26 colon carcinoma cells in Balb/c mice. Third, the expression of alpha smooth muscle actin, caspase-3 and Ki-67 expression was quantified by immunohistochemistry, then gene expression levels of inflammatory factors were measured by quantitative RT-PCR. According to our results, OOS reduced tumor cell viability and migration in vitro. Moreover, in vivo daily administration of OOS from the 7th day after tumor cell inoculation decreased the total area and size of metastatic foci in the liver. Furthermore, cell proliferation and fibroblast recruitment was decreased in tumor foci while a higher number of apoptotic cells were observed. Finally, RNA levels for the inflammatory mediators COX-2, IFNγ, IL1β, IL6 and TNFα were reduced in total liver. In conclusion, OOS reduced the metastatic development of colorectal cancer to the liver by increasing apoptosis, and decreasing tumor cell proliferation and fibroblast recruitment in the tumor foci, as well as the expression of inflammatory mediators in total liver. These results point out OOS as a potential supplement to be applied as complementary therapy for the treatment of liver metastasis from colorectal cancer.

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“…[68] Westernb lot, immunohistochemistry, immunofluorescence, andE LISA have been widely used in the detection of these proteins released to cytosol. [69][70][71][72] These methods exhibit high sensitivity;h owever,t hey involvem ultiple steps;t ime-consuming processes; require large, expensive instruments;e xtensive pretreatment of the sample;a nd are also not suitable for rapid routine use.…”

Section: Protein Releasementioning

confidence: 99%

Apoptosis Evaluation by Electrochemical Techniques

Yin

2015

Chemistry An Asian Journal

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Apoptosis has close relevance to pathology, pharmacology, and toxicology. Accurate and convenient detection of apoptosis would be beneficial for biological study, clinical diagnosis, and drug development. Based on distinct features of apoptotic cells, a diversity of analytical techniques have been exploited for sensitive analysis of apoptosis, such as surface plasmon resonance, electrochemical methods, flow cytometry, and some imaging assays. Among them, the features of simplicity, easy operation, low cost, and high sensitivity make electrochemical techniques powerful tools to investigate electron-transfer processes of in vitro biological systems. In this contribution, a general overview of current knowledge on various technical approaches for apoptosis evaluation is provided. Furthermore, recently developed electrochemical biosensors for detecting apoptotic cells and their advantages over traditional methods are summarized. One of the main considerations focuses on designing the recognition elements based on various biochemical events during apoptosis.

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α-Terthienylmethanol, isolated from Eclipta prostrata, induces apoptosis by generating reactive oxygen species via NADPH oxidase in human endometrial cancer cells

Cited by 28 publications

References 50 publications

Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway

Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway

Ocoxin® oral solution slows down tumor growth in an experimental model of colorectal cancer metastasis to the liver in Balb/c mice

Apoptosis Evaluation by Electrochemical Techniques

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