Glibenclamide induces apoptosis by activating reactive oxygen species dependent JNK pathway in hepatocellular carcinoma cells

Yan, Bin; Peng, Zhiyong; Xiao, Xing; Du, Chunling

doi:10.1042/bsr20170685

Cited by 21 publications

(17 citation statements)

References 21 publications

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“…Secondly, glipizide inhibits endothelial cell migration and tubular formation via up-regulating the expression of natriuretic peptide receptor A to suppress tumor angiogenesis [37,38]. Thirdly, glibenclamide significantly induces HCC cell apoptosis via activating reactive-oxygen-species-dependent JNK pathway [39] and arrests HCC growth [40]. Fourthly, sitagliptin and vildagliptin trigger the infiltration of natural killer cells and T-cells into xenograft or liver tumors in rodent models [41].…”

Section: Plos Onementioning

confidence: 99%

Prognostic roles of diabetes mellitus and hypertension in advanced hepatocellular carcinoma treated with sorafenib

et al. 2020

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Background & aims It remains limited whether diabetes mellitus (DM) and hypertension (HTN) affect the prognosis of advanced hepatocellular carcinoma (HCC) treated with sorafenib. Our study attempted to elucidate the roles of DM/HTN and the effects of diabetes medications among advanced HCC patients receiving sorafenib. Methods From August 2012 to February 2018, 733 advanced HCC patients receiving sorafenib were enrolled at China Medical University, Taichung, Taiwan. According to the presence/absence of DM or HTN, they were divided into four groups: control [DM(-)/HTN(-), n = 353], DM-only [DM(+)/HTN(-), n = 91], HTN-only [DM(-)/HTN(+), n = 184] and DM+HTN groups [DM(+)/HTN(+), n = 105]. Based on the types of diabetes medications, there were three groups among DM patients (the combined cohort of DM-only and DM+HTN groups), including metformin (n = 63), non-metformin oral hypoglycemic agent (OHA) (n = 104) and regular insulin (RI)/neutral protamine hagedorn (NPH) groups (n = 29). We then assessed the survival differences between these groups. Results DM-only and DM+HTN groups significantly presented longer overall survival (OS) than control group (control vs. DM-only, 7.70 vs. 11.83 months, p = 0.003; control vs. DM+HTN, 7.70 vs. 11.43 months, p = 0.008). However, there was no significant OS difference between control and HTN-only group (7.70 vs. 8.80 months, p = 0.111). Besides, all groups of DM patients showed significantly longer OS than control group (control vs. metformin, 7.70 vs. 12.60 months, p = 0.011; control vs. non-metformin OHA, 7.70 vs. 10.80 months, p = 0.016; control vs. RI/NPH, 7.70 vs. 15.20 months, p = 0.026). Conclusions Rather than HTN, DM predicts better prognosis in advanced HCC treated with sorafenib. Besides, metformin, non-metformin OHA and RI/NPH are associated with longer survival among DM-related advanced HCC patients receiving sorafenib.

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Section: Plos Onementioning

confidence: 99%

Prognostic roles of diabetes mellitus and hypertension in advanced hepatocellular carcinoma treated with sorafenib

et al. 2020

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“…In order to test the effect of GPM on KEGG pathways at the individual gene level, we mapped DEGs in cells treated with GPM on protein processing in ER (Figure 5 A). Persistent oxidative stress plays an important factor in mediating ERS and may become the inducer of ERS 19 - 21 . GPM attenuated the generation of ROS in HepG2 cells (Figure 5 B and 5 C).…”

Section: Resultsmentioning

confidence: 99%

Differentially expressed genes of HepG2 cells treated with gecko polypeptide mixture

et al. 2018

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Gecko (Gekko japonicus) extracts have been used in traditional Chinese medicine for many years. It has been proven that the gecko polypeptide mixture (GPM) extracted from gecko can inhibit the growth of multiple types of tumor cells. In order to investigate the possible anti-tumor molecular mechanisms of GPM, we used RNA-seq technology to identify the differentially expressed genes (DEGs) of human hepatocellular carcinoma (HCC) HepG2 cells treated with or without GPM. MTT assay was used to detect the viability of HepG2 cells. DAPI fluorescence staining was performed to observe morphological changes in the nuclei of HepG2 cells. Western blot analysis was applied to observe the expressions of apoptosis-related and endoplasmic reticulum stress (ERS)-related proteins in HepG2 cells. Flow cytometry assay was performed to detect the apoptosis and reactive oxygen species (ROS) in HepG2 cells. Our results showed that GPM inhibited HepG2 cells proliferation and induced the apoptosis of HepG2 cells. RNA-seq analysis suggested that the ER-nucleus signaling pathway involved in the anti-cancer molecular mechanism of GPM. Therefore, GPM may induce apoptosis in HepG2 cells via the ERs pathway.

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“…In our study, ZO effectively induced oxidative stress to mediate alteration of outer MMP, indicating diminished fluorescence intensity in a concentration‐dependent manner. Plant‐based phenolic agents strongly generates ROS, which could lead to inducing MMP alteration and its dependent proapoptotic nature . Another study documented that ginger extract induced oxidative stress‐mediated membrane potential changes and signaling activation in HT1080 cells …”

Section: Discussionmentioning

confidence: 99%

A ginger derivative, zingerone—a phenolic compound—induces ROS‐mediated apoptosis in colon cancer cells (HCT‐116)

Veeraraghavan

Mohan

et al. 2019

J Biochem & Molecular Tox

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Zingerone (ZO), an active phenolic agent derived from Zingiber officinale (Ginger), has many pharmacological properties such as antioxidant, antiangiogenic, and antitumor. However, its potential value in cancer and the mechanism by which ZO wields its therapeutic effects remain obscure. Therefore, in this current study, we explored the effects of ZO on suppressing cell proliferation and enhancing apoptosis in colon cancer cells (HCT116). Our results indicated that ZO significantly enhances the production of reactive oxygen species, lipid peroxidation (thiobarbituric acid reactive substance [TBARS]), and loss of cell viability; and reduces mitochondrial membrane potential and antioxidant levels (SOD, CAT, and GSH) in ZO‐treated HCT116 cells in a dose‐dependent (2.5, 5, and 10 µM) manner. Furthermore, ZO induces oxidative stress‐mediated apoptosis as evidenced by apoptotic morphological changes predicted by AO/EtBr, Hoechst staining and further confirmed by comet assay. Moreover, immunoblotting techniques showed that ZO treatment effectively enhances Bax, caspase‐9, and caspase‐3 expressions and decreases the expression of Bcl‐2 in colon cancer cells. Together, our results evidenced that the antitumor effects of ZO reduce cell proliferation and stimulate apoptosis through modulating pro‐ and antiapoptotic molecular events in HCT116 colon cancer cells. Therefore, based on our findings, ZO may be used as a therapeutic agent for the treatment of colon cancer.

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Glibenclamide induces apoptosis by activating reactive oxygen species dependent JNK pathway in hepatocellular carcinoma cells

Cited by 21 publications

References 21 publications

Prognostic roles of diabetes mellitus and hypertension in advanced hepatocellular carcinoma treated with sorafenib

Prognostic roles of diabetes mellitus and hypertension in advanced hepatocellular carcinoma treated with sorafenib

Differentially expressed genes of HepG2 cells treated with gecko polypeptide mixture

A ginger derivative, zingerone—a phenolic compound—induces ROS‐mediated apoptosis in colon cancer cells (HCT‐116)

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