CXC195 induces apoptosis and endoplastic reticulum stress in human hepatocellular carcinoma cells by inhibiting the PI3K/Akt/mTOR signaling pathway.

Abstract:

:CXC195 exhibits strong protective effects against neuronal apoptosis by exerting antioxidant activity. However, the pharmacological function of CXC195 in cancer remains to be elucidated. The present study demonstrated that CXC195 exhibited significant cytotoxic effects, and induced cell cycle arrest and apoptosis in HepG2 human hepatocellular carcinoma (HCC) cell lines. Following treatment of HepG2 cells with 150 µΜ CXC195 for 24 , cell viability and the apoptotic rate were assessed using an MTT assay and Annexin V/propidium iodide staining followed by flow cytometric analysis. Molecular markers of the cell cycle, apoptosis, mitochondrial function and endoplasmic reticulum (ER) stress were analyzed by western blot or polymerase chain reaction analysis. Caspase activation, cytochrome c and apoptosis‑inducing factor release, and analysis of the B cell lymphoma 2 (Bcl‑2)‑associated X protein/Bcl‑2 ratio demonstrated that the anticancer effects of CXC195 in HepG2 cells were mediated by caspase and mitochondria‑dependent apoptosis. CXC195 also induced the expression of ER stress‑associated proteins, including CCAAT‑enhancer‑binding protein homologous protein, and glucose‑regulated proteins 94 and 78, and led to the activation of multiple branches of ER stress transducers, including inositol‑requiring enzyme 1α‑apoptosis signal‑regulating kinase‑p38/c‑Jun N‑terminal kinase, and protein kinase R‑like endoplasmic reticulum kinase‑eukaryotic translation initiation factor 2α‑activating transcription factor (ATF)4 and ATF6, in the HepG2 cells. In addition, CXC195 inhibited the phosphorylation of phosphoinositide 3‑kinase (PI3K), Akt and mammalian target of rapamycin (mTOR) in the HepG2 cells. These effects were enhanced following treatment with selected inhibitors of PI3K (LY294002), Akt (SH‑6) and mTOR (rapamycin). Furthermore, these inhibitors enhanced the pro‑apoptotic effects of CXC195 in the HepG2 cells. In conclusion, the results of the present study indicated that CXC195 induced apoptosis and ER stress in HepG2 cells through the inhibition of the PI3K/Akt/mTOR signaling pathway.

journal_name

Mol Med Rep

authors

Chen XL,Fu JP,Shi J,Wan P,Cao H,Tang ZM

doi

10.3892/mmr.2015.4479

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

8229-36

issue

6

eissn

1791-2997

issn

1791-3004

journal_volume

12

pub_type

杂志文章
  • MG132 reverse the malignant characteristics of hypopharyngeal cancer.

    abstract::In order to reverse the malignant characteristics of hypopharyngeal cancer, the proteasome inhibitor MG132 was introduced into FaDu/T cells and the mechanisms underlying its effects were investigated. The multi-drug resistance (MDR) sensitivities of FaDu/T and FaDu/T-MG132 cancer cells to several chemotherapeutics wer...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2014.2103

    authors: Ma J,Yu L,Tian J,Mu Y,Lv Z,Zou J,Li J,Wang H,Xu W

    更新日期:2014-06-01 00:00:00

  • Plasma heme oxygenase-1 is decreased in peripheral artery disease patients.

    abstract::Peripheral artery disease (PAD) is a common manifestation of atherosclerosis. A number of emerging risk factors, including oxidative stress biomarkers, free radicals and heat shock proteins, may add to the established risk factors for cardiovascular disease (CVD). The present study assessed surrogate markers of oxidat...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2016.5644

    authors: Signorelli SS,Li Volsi G,Fiore V,Mangiafico M,Barbagallo I,Parenti R,Rizzo M,Li Volti G

    更新日期:2016-10-01 00:00:00

  • Wound healing effect of an Astragalus membranaceus polysaccharide and its mechanism.

    abstract::In the present study, a novel polysaccharide, APS2-1, was isolated and purified from Astragalus membranaceus using DEAE-cellulose and Sephadex G-100 chromatography. The effect of APS2‑1 on the promotion of wound healing was evaluated and its preliminary mechanism was investigated. In vitro experiments showed that APS2...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2017.6488

    authors: Zhao B,Zhang X,Han W,Cheng J,Qin Y

    更新日期:2017-06-01 00:00:00

  • CIZ1 regulates the proliferation, cycle distribution and colony formation of RKO human colorectal cancer cells.

    abstract::Cip1-interacting zinc finger protein 1 (CIZ1) is a nuclear protein that was observed to bind to p21Cip1/Waf1. p21Cip1/Waf1 regulates the cell cycle and is associated with colorectal cancer (CRC) progression. However, the effect of CIZ1 on CRC cells remains unclear. In the present study, CIZ1 was observed to be highly ...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2013.1716

    authors: Yin J,Wang C,Tang X,Sun H,Shao Q,Yang X,Qu X

    更新日期:2013-12-01 00:00:00

  • EphA2‑enriched exosomes promote cell migration and are a potential diagnostic serum marker in pancreatic cancer.

    abstract::Pancreatic cancer (PC) is the fourth most common cause of cancer‑related mortality worldwide and is characterized by high invasiveness and early metastasis. To identify novel diagnostic markers, the present study aimed to understand the mechanism underlying PC progression. The present study demonstrated that exosomes ...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2020.11384

    authors: Wei Q,Wei L,Zhang J,Li Z,Feng H,Ren L

    更新日期:2020-10-01 00:00:00

  • Study of the effect of miR‑124 and the SOX9 target gene in Hirschsprung's disease.

    abstract::Hirschsprung's disease (HSCR) is a polygenic disease, of which the cause remains to be elucidated. It has been suggested that SRY-related HMG-box 9 (SOX9) is fundamental for the correct development of oligodendrocytes and astrocytes; however, not the development of neurons. There are currently no reports regarding SOX...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2014.2022

    authors: Mi J,Chen D,Wu M,Wang W,Gao H

    更新日期:2014-05-01 00:00:00

  • Propranolol suppresses the proliferation and induces the apoptosis of liver cancer cells.

    abstract::An increasing amount of evidence indicates that the inhibition of β adrenergic signaling can result in the inhibition of tumor growth. However, the role of propranolol in liver cancer and the underlying mechanism remain to be elucidated. The present study aimed to investigate the role of propranolol in liver cancer ce...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2018.8476

    authors: Wang F,Liu H,Wang F,Xu R,Wang P,Tang F,Zhang X,Zhu Z,Lv H,Han T

    更新日期:2018-04-01 00:00:00

  • Stathmin is key in reversion of doxorubicin resistance by arsenic trioxide in osteosarcoma cells.

    abstract::Osteosarcoma is the most common type of malignant bone tumor in children and adolescents. Numerous patients are unable to be cured due to the development of resistance of the osteosarcoma cells to chemotherapeutic drugs. Therefore, reversion of drug resistance is urgently required for the treatment of osteosarcoma. Ar...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2014.2618

    authors: Feng T,Qiao G,Feng L,Qi W,Huang Y,Yao Y,Shen Z

    更新日期:2014-12-01 00:00:00

  • Lutein protects against severe traumatic brain injury through anti‑inflammation and antioxidative effects via ICAM‑1/Nrf‑2.

    abstract::Many studies have reported that lutein may exert its biological activities, including anti‑inflammation, anti‑oxidase and anti‑apoptosis, through effects on reactive oxygen species (ROS). Thus, lutein may prevent the damaging activities of ROS in cells. The current study investigated the effect of lutein against sever...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2017.7040

    authors: Tan D,Yu X,Chen M,Chen J,Xu J

    更新日期:2017-10-01 00:00:00

  • Biological effects of eukaryotic recombinant plasmid pReceiver-M61-BAI-1 transfection on T24 cells and HUVECs.

    abstract::The aim of the current study was to investigate the biological effect on T24 cells and human umbilical vein endothelial cells (HUVECs) of transfection with brain-specific angiogenesis inhibitor-1 (BAI-1). The recombinant plasmid pReceiver-M61-BAI-1 was transfected into human superficial bladder tumor cells (T24) and H...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2016.5422

    authors: Tian DW,Hu HL,Sun Y,Tang Y,Lei MD,Liu LW,Han RF,Wu CL

    更新日期:2016-08-01 00:00:00

  • BmK CT and 125I-BmK CT suppress the invasion of glioma cells in vitro via matrix metalloproteinase-2.

    abstract::Chlorotoxin (CTX) is an established blocker of small‑conductance Cl‑ channels and has previously been demonstrated to inhibit the invasion of glioma cells. Buthus martensii Karsch chlorotoxin‑like toxin (BmK CT) is the first chlorotoxin-like peptide. The present study aimed to determine the inhibitory effect of BmK CT...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2017.6284

    authors: Sun N,Zhao L,Qiao W,Xing Y,Zhao J

    更新日期:2017-05-01 00:00:00

  • Recombinant Ganoderma lucidum immunomodulatory protein modified with polyethylene glycol.

    abstract::Recombinant Ganoderma lucidum immunomodu-latory protein (rLZ-8) expressed using the Pichia yeast eukaryotic expression system is a potential new drug for cancer therapy; however, it has a short half-life in the body. In order to optimize the potency and stability of rLZ-8, we modifi...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2013.1281

    authors: Zhang X,Sun F,Liu Z,Zhang S,Liang C

    更新日期:2013-03-01 00:00:00

  • AlloDerm implants for prevention of Frey syndrome after parotidectomy: a systematic review and meta-analysis.

    abstract::Although Frey syndrome is not life-threatening, it is identified as the most serious and widely recognized sequela of parotidectomy and has significant potential negative social and psychological implications. Several studies have investigated whether AlloDerm® implants prevent Frey syndrome effectively and safely, ho...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章,meta分析,评审

    doi:10.3892/mmr.2012.762

    authors: Zeng XT,Tang XJ,Wang XJ,Li MZ,Guo Y,Huang W,Niu YM,Leng WD

    更新日期:2012-04-01 00:00:00

  • Hepatitis B virus inhibits the expression of CD82 through hypermethylation of its promoter in hepatoma cells.

    abstract::The tumor suppressor gene CD82, also known as KAI1, may act as a general suppressor of metastasis in numerous types of cancer. It is hypothesized that downregulation of CD82 gene expression may be an important factor in the induction of hepatocellular carcinoma (HCC), however the mechanism for this requires further st...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2014.2495

    authors: Yu G,Bing Y,Li W,Xia L,Liu Z

    更新日期:2014-11-01 00:00:00

  • Inhibition of TLR4 protects rat islets against lipopolysaccharide-induced dysfunction.

    abstract::Oxidative stress leads to dysfunction in pancreatic cells, causing a reduction in insulin secretion following exposure to glucose. Toll-like receptor 4 (TLR4) may be activated by exposure to lipopolysaccharide (LPS) stress. TLR4 may mediate the initiation of inflammatory and immune defense responses; however, the impo...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2016.6097

    authors: Wang X,Ge QM,Bian F,Dong Y,Huang CM

    更新日期:2017-02-01 00:00:00

  • Histone acetylation is involved in TCDD‑induced cleft palate formation in fetal mice.

    abstract::The aim of the present was to evaluate the effects of DNA methylation and histone acetylation on 2,3,7,8‑tetrachlorodibenzo‑p‑dioxin (TCDD)‑induced cleft palate in fetal mice. Pregnant mice (n=10) were randomly divided into two groups: i) TCDD group, mice were treated with 28 µg/kg TCDD on gestation day (GD) 10 by ora...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2016.5348

    authors: Yuan X,Qiu L,Pu Y,Liu C,Zhang X,Wang C,Pu W,Fu Y

    更新日期:2016-08-01 00:00:00

  • Rapid and sensitive detection of Plesiomonas shigelloides by cross‑priming amplification of the hugA gene.

    abstract::Plesiomonas shigelloides (P. shigelloides) is implicated as an aetiological agent of human gastroenteritis in humans, for which reliable laboratory detection of P. shigelloides is clinically and epidemiologically desirable. A simple molecular method for rapid detection of P. shigelloides using cross‑priming amplificat...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2016.5937

    authors: Meng S,Wang Y,Wang Y,Ye C

    更新日期:2016-12-01 00:00:00

  • Alogliptin alleviates hepatic steatosis in a mouse model of nonalcoholic fatty liver disease by promoting CPT1a expression via Thr172 phosphorylation of AMPKα in the liver.

    abstract::Pioglitazone (PIO) has been reported to be effective for nonalcoholic fatty liver disease (NAFLD) and alogliptin (ALO) may have efficacy against NAFLD progression in patients with type 2 diabetes mellitus (T2DM). The present study examined the effectiveness of ALO in a rodent model of NAFLD and diabetes mellitus. KK‑A...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2018.8673

    authors: Tobita H,Sato S,Yazaki T,Mishiro T,Ishimura N,Ishihara S,Kinoshita Y

    更新日期:2018-05-01 00:00:00

  • Role of long noncoding RNAs in malignant disease (Review).

    abstract::Long noncoding RNAs (lncRNAs) are endogenous transcribed RNA molecules without protein-coding potential, ranging between 200 and 100,000 nt in length. LncRNAs regulate the expression of specific genes in several ways, including guiding chromatin-remodeling, and affecting splicing, transcription or translation. The mut...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章,评审

    doi:10.3892/mmr.2015.4711

    authors: Li Y,Wang X

    更新日期:2016-02-01 00:00:00

  • Von Hippel-Lindau gene expression on the human fallopian tube epithelium during the menstrual cycle.

    abstract::The Von Hippel-Lindau gene (VHL) is a tumor suppressor gene, which is widely expressed in kidney, lung, breast, ovary, and cervix. VHL gene mutations can induce VHL disease and tumorigenesis. However, whether this gene is expressed in the human fallopian tube has not been evaluated. The objectives of this study were t...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2015.3237

    authors: Lu YY,Zhu WJ,Xie BG

    更新日期:2015-06-01 00:00:00

  • [Corrigendum] Molecular mechanism of extracellular matrix disorder in pelvic organ prolapses.

    abstract::Subsequently to the publication of the above article, the authors have realized that the bar charts shown for Fig. 3A and B, as they appeared in the paper, were the same as the bar charts shown for Fig. 4B and D. Fig. 3, as it should have appeared, is shown below. All the authors agree to this Corrigendum. Note that t...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2020.11721

    authors: Zhang L,Dai F,Chen G,Wang Y,Liu S,Zhang L,Xian S,Yuan M,Yang D,Zheng Y,Deng Z,Cheng Y,Yang X

    更新日期:2021-01-01 00:00:00

  • Integrated analysis of genome‑wide gene expression and DNA methylation microarray of diffuse large B‑cell lymphoma with TET mutations.

    abstract::Diffuse large B-cell lymphoma (DLBCL), the most frequently occurring type of lymphoid malignancy, has been demonstrated to be associated with mutations of Ten‑Eleven Translocation (TET). In order to explore the association between DLBCL and TET mutations, the present study analyzed the gene expression and methylation ...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2017.7058

    authors: Liu P,Jiang W,Zhao J,Zhang H

    更新日期:2017-10-01 00:00:00

  • Expression of pancreatic regenerating gene in lung and intestinal tissue correlates with the severity of disease in rats with acute necrotizing pancreatitis.

    abstract::The aim of this study was to investigate the expression pattern of regenerating gene I (Reg I) in the lung and intestinal tissues of rats with acute necrotizing pancreatitis (ANP), as well as the correlation of Reg I expression with lung and intestinal injury. Sprague-Dawley rats were randomly allocated to control (n=...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2012.1187

    authors: Hu HL,Zhang Q,Kong B,Shi X

    更新日期:2013-02-01 00:00:00

  • Raloxifene neutralizes the adverse effects of glutamate on cultured neurons by regulation of calcium oscillations.

    abstract::Calcium dyshomeostasis is an important pathology of memory impairment. However, the mechanism of how calcium dyshomeostasis impairs neurons has remained elusive. The aim of the present study was to reveal the influence of calcium dyshomeostasis on the expression of calcium memory‑associated proteins and the ability of...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2015.4191

    authors: Zhou X,Yang Z,Han L,Li X,Feng M,Zhang T,Luo H,Zhu L,Zhang J,Zhang Q,Hu Q

    更新日期:2015-10-01 00:00:00

  • β-Elemene inhibits proliferation through crosstalk between glia maturation factor β and extracellular signal‑regulated kinase 1/2 and impairs drug resistance to temozolomide in glioblastoma cells.

    abstract::β-elemene, a plant-derived drug extracted from Curcuma wenyujin, has demonstrated marked antiproliferative effects on glioblastoma, while toxicity remains low. However, the underlying molecular mechanisms of the antitumor activity of β-elemene remain to be elucidated. Previously, it was identified that the glia matura...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2014.2273

    authors: Zhu TZ,Li XM,Luo LH,Xu YH,Cao P,Liu Y,Liang GB

    更新日期:2014-08-01 00:00:00

  • Erythropoietin reduces brain injury after intracerebral hemorrhagic stroke in rats.

    abstract::Erythropoietin (EPO) has been shown to be neuroprotective in various models of neuronal injury. The aim of the present study was to investigate the beneficial effect of recombinant human EPO (rhEPO) following intracerebral hemorrhage (ICH) and the underlying molecular and cellular mechanisms. ICH was induced using aut...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2013.1666

    authors: Yu Z,Tang L,Chen L,Li J,Wu W,Hu C

    更新日期:2013-11-01 00:00:00

  • Quercetin-mediated apoptosis via activation of the mitochondrial-dependent pathway in MG-63 osteosarcoma cells.

    abstract::Quercetin (a natural polyphenolic compound) is a polyphenolic flavonoid compound found in a variety of plants. It has been demonstrated to exert cytostatic activity against a variety of human cancer cell lines, including the human osteosarcoma cell line, MG-63. However, its effects on osteosarcoma cell apoptosis are s...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2011.533

    authors: Liang W,Li X,Li C,Liao L,Gao B,Gan H,Yang Z,Liao L,Chen X

    更新日期:2011-09-01 00:00:00

  • Effects of cyclin E gene silencing on the proliferation of esophageal cancer cell lines, EC9706, Eca109 and KYSE30.

    abstract::In order to observe the effects of cyclin E gene silencing by small interfering RNA (siRNA) on the growth, proliferation, invasion and apoptosis of esophageal cancer cell lines, including EC9706, Eca109 and KYSE30, siRNA vectors targeting cyclin E gene were constructed and then tran...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2013.1280

    authors: Wang N,Li M,Zang WQ,Ma YY,Wang YY,Zhao GQ

    更新日期:2013-03-01 00:00:00

  • TRESK gene recombinant adenovirus vector inhibits capsaicin-mediated substance P release from cultured rat dorsal root ganglion neurons.

    abstract::The present study was conducted to determine whether the activation of TRESK in the dorsal root ganglion (DRG) by the TRESK gene recombinant adenovirus vector inhibits the capsaicin-evoked substance P (SP) release using a radioimmunoassay. TRESK is an outwardly rectifying K+ current...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2012.778

    authors: Zhou J,Yao SL,Yang CX,Zhong JY,Wang HB,Zhang Y

    更新日期:2012-04-01 00:00:00

  • miR‑107 promotes the erythroid differentiation of leukemia cells via the downregulation of Cacna2d1.

    abstract::microRNAs (miRNAs) have been reported to be involved in various human diseases. They may have uses in diagnosis and as therapeutic targets, thus the discovery of novel miRNAs has the potential to provide clinical tools or shed light on novel mechanisms. In the current study, miR‑107 was revealed to be downregulated in...

    journal_title:Molecular medicine reports

    pub_type: 杂志文章

    doi:10.3892/mmr.2014.2865

    authors: Ruan J,Liu X,Xiong X,Zhang C,Li J,Zheng H,Huang C,Shi Q,Weng Y

    更新日期:2015-02-01 00:00:00