AZD8055 induces cell death associated with autophagy and activation of AMPK in hepatocellular carcinoma.

Abstract:

:AZD8055 is a potent inhibitor of mTORC1 and mTOR2 and shows inhibitory effects in several types of cancer cells in vitro and in vivo. However, the effect of AZD8055 on hepatocellular carcinoma (HCC) cells has not been studied. We report that AZD8055 inhibits cell proliferation and colony formation of Hep3B and Huh7 cells but does not cause PARP cleavage, or caspase activation, suggesting that classical apoptosis is not its main mechanism of cell death. By contrast, AZD8055-induced cell death was associated with several characteristics of autophagy, including an increase in acidic vesicular organelle content, conversion of cytosolic LC3-I to membrane-bound LC3-II and elevation of the levels of Atg-5/12, BECN1 and LC3-II. Inhibition of autophagy by 3-methyladenine (3-MA) partially inhibited AZD8055-induced cell death. Furthermore, AZD8055 caused the activation of AMPK and co-treatment with the AMPK inhibitor dorsomorphin also caused a partial but significant reduction of AZD8055-induced cell death. In conclusion, AZD8055-induced HCC cell death is associated with induction of autophagy and activation of AMPK.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Hu M,Huang H,Zhao R,Li P,Li M,Miao H,Chen N,Chen M

doi

10.3892/or.2013.2890

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

649-56

issue

2

eissn

1021-335X

issn

1791-2431

journal_volume

31

pub_type

杂志文章
  • Factors influencing the detection of the BRAF T1799A mutation in papillary thyroid carcinoma.

    abstract::The BRAF T1799A mutation is a heterozygous point mutation and its reported prevalence in papillary thyroid carcinoma (PTC) has varied from 29 to 83%, with an overall mean of 44%. In Korea, the reported mutation rate reached 83% in PTC and 52% in micropapillary carcinoma. We hypothesized that the differences in prevale...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2011.1225

    authors: Kim HS,Kim JO,Lee DH,Lee HC,Kim HJ,Kim JH,Jang YS,Lee JM,Kim SY,Kim YS

    更新日期:2011-06-01 00:00:00

  • STAT3 inhibition by WP1066 suppresses the growth and invasiveness of bladder cancer cells.

    abstract::Signal transducer and activator of transcription 3 (STAT3) regulates the expression of genes mediating cell survival, proliferation and angiogenesis and is aberrantly activated in various types of malignancies, including bladder cancer. We examined whether it could be a novel therapeutic target for bladder cancer usin...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.5902

    authors: Tsujita Y,Horiguchi A,Tasaki S,Isono M,Asano T,Ito K,Asano T,Mayumi Y,Kushibiki T

    更新日期:2017-10-01 00:00:00

  • Phosphorylation state of tumor-suppressor gene p53 product overexpressed in skin tumors.

    abstract::Post-transcriptional modification of p53 by phosphorylation has been proposed as an important mechanism of p53 stabilization and functional regulation. However, little is known about the phosphorylation state of mutant p53 protein overexpressed in human tumors. We evaluated immunohistochemically the p53 phosphorylatio...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Matsumoto M,Furihata M,Kurabayashi A,Ohtsuki Y

    更新日期:2004-11-01 00:00:00

  • Identification and characterization of sexual dimorphism‑linked gene expression profile in hepatocellular carcinoma.

    abstract::Hepatocellular carcinoma (HCC) is sexually disparate in humans, with a significantly increased prevalence in males. The molecular mechanisms by which the inhibition or development of liver cancer are facilitated require further investigation with regard to sex factors affecting disease progression. In the present stud...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2019.7217

    authors: Wu Y,Yao N,Feng Y,Tian Z,Yang Y,Zhao Y

    更新日期:2019-09-01 00:00:00

  • Over-regulation of microRNA-133b inhibits cell proliferation of cisplatin-induced non-small cell lung cancer cells through PI3K/Akt and JAK2/STAT3 signaling pathway by targeting EGFR.

    abstract::The present study determined the anticancer activity and its mechanism of microRNA‑133b on cell proliferation of cisplatin-induced non-small cell lung cancer cells. The expression of microRNA-133b cisplatin‑induced non-small cell lung cancer (NSCLC) tissue was lower than that of para-carcinoma tissue in patients. Over...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6215

    authors: Li B,Ding CM,Li YX,Peng JC,Geng N,Qin WW

    更新日期:2018-03-01 00:00:00

  • Role of 4‑aminobutyrate aminotransferase (ABAT) and the lncRNA co‑expression network in the development of myelodysplastic syndrome.

    abstract::IncRNAs play an important role in the regulation of gene expression. The present study profiled differentially expressed lncRNAs (DELs) and mRNAs (DEMs) in myelodysplastic syndrome (MDS) to construct a 4‑aminobutyrate aminotransferase (ABAT)‑DEL‑DEM co‑expression network in MDS development using the Agilent human Bead...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2019.7175

    authors: Chen Y,Zhao G,Li N,Luo Z,Wang X,Gu J

    更新日期:2019-08-01 00:00:00

  • Isolation and characterization of lymphatic endothelial cells from human glossal lymphangioma.

    abstract::Abnormal lymphangiogenesis is associated with several diseases such as tumor metastasis and lymphangioma. Human lymphangioma originated from the transformation of lymphatic endothelium is a benign malformation of lymphatic vessels and its pathogenesis has up to date not been illuminated and its cell model has also not...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: You L,Wu M,Chen Y,Xu G,Wei J,Li Q,Song A,Zhao L,Li S,Han Z,Zhou J,Lu Y,Wang S,Ma D,Meng L

    更新日期:2010-01-01 00:00:00

  • REV3L modulates cisplatin sensitivity of non-small cell lung cancer H1299 cells.

    abstract::Lung cancer remains the leading cause of cancer-related mortality worldwide and non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all cases of lung cancer. Cisplatin plays a significant role in the management of human lung cancer. Translesion DNA synthesis (TLS) is involved in DNA damage repair. ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4121

    authors: Wang W,Sheng W,Yu C,Cao J,Zhou J,Wu J,Zhang H,Zhang S

    更新日期:2015-09-01 00:00:00

  • Identification of molecular candidates and interaction networks via integrative toxicogenomic analysis in a human cell line following low-dose exposure to the carcinogenic metals cadmium and nickel.

    abstract::Cadmium and nickel have been classified as carcinogenic to humans by the World Health Organization's International Agency for Research on Cancer. Given their prevalence in the environment, the fact that cadmium and nickel may cause diseases including cancer even at low doses is a cause for concern. However, the exact ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2587

    authors: Kwon JY,Weon JI,Koedrith P,Park KS,Kim IS,Seo YR

    更新日期:2013-09-01 00:00:00

  • Multivariate analysis of metastasis‑related risk factors for patients with gastroenteropancreatic neuroendocrine tumors based on clinicopathological and endoscopic features.

    abstract::Gastroenteropancreatic neuroendocrine tumors (GEP‑NETs) are relatively uncommon. Unfortunately, epidemiological studies on the incidence of GEP‑NETs worldwide have reported a marked increase in the detection of these tumors. Although they often exhibit relatively indolent clinical courses, GEP‑NETs have the potential ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.5170

    authors: Tang C,Gong L,Zou W,Zhang J,Zhou Y,Wu X,Lu F,Ouyang C,Liu X

    更新日期:2016-12-01 00:00:00

  • Serenoa repens induces growth arrest and apoptosis of human multiple myeloma cells via inactivation of STAT 3 signaling.

    abstract::Serenoa repens, a palm species native to the Southeastern United States, is one of the widely used phytotherapeutic agents in benign prostatic hyperplasia. In this study, we found for the first time that Serenoa repens induced growth arrest of a variety of human leukemia cells including U266 and RPMI 8226 multiple mye...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Che Y,Hou S,Kang Z,Lin Q

    更新日期:2009-08-01 00:00:00

  • Sunitinib in patients with metastatic renal cell carcinoma: Birmingham experience.

    abstract::Sunitinib is a novel, multi-targeted receptor tyrosine kinase inhibitor, which has demonstrated evidence of improved survival when compared to interferon (IFN)-alpha in patients with metastatic renal cell carcinoma (RCC). Recently published National Institute for Health and Clinical Excellence guidance recommends suni...

    journal_title:Oncology reports

    pub_type: 临床试验,杂志文章

    doi:10.3892/or_00000886

    authors: Ansari J,Fatima A,Fernando K,Collins S,James ND,Porfiri E

    更新日期:2010-08-01 00:00:00

  • Induction and mechanism of HeLa cell apoptosis by 9-oxo‑10, 11-dehydroageraphorone from Eupatorium adenophorum.

    abstract::9-Oxo-10, 11-dehydroageraphorone (euptox A), a cadenine sesquiterpene, is the main toxin from Eupatorium adenophorum. The aim of the present study was to examine the induction and mechanism of HeLa cell apoptosis by euptox A. The apoptosis‑inducing effect of the euptox A on HeLa cells was examined by MTT assay. The un...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.3778

    authors: Liao F,Hu Y,Wu L,Tan H,Luo B,He Y,Qiao Y,Mo Q,Wang Y,Zuo Z,Deng J,Wei Y

    更新日期:2015-04-01 00:00:00

  • Forced downregulation of RACK1 inhibits glioma development by suppressing Src/Akt signaling activity.

    abstract::Glioma is the most common primary brain malignant tumor. Receptor for activated C-kinase 1 (RACK1) is widely expressed in the central nervous system, and regulates multiple cellular processes including cell survival, proliferation, migration and metastasis. However, the role of RACK1 in glioma has never been revealed....

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2723

    authors: Peng R,Jiang B,Ma J,Ma Z,Wan X,Liu H,Chen Z,Cheng Q,Chen R

    更新日期:2013-11-01 00:00:00

  • Isothiocyanates repress estrogen receptor alpha expression in breast cancer cells.

    abstract::The isothiocyanates (ITCs) have long been known to possess chemopreventive activities for a variety of neoplasms including breast cancer, but the molecular mechanism by which ITCs prevent breast cancer development has not been established. In this study, we investigated the effects of benzyl and phenethyl isothiocyana...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Kang L,Ding L,Wang ZY

    更新日期:2009-01-01 00:00:00

  • Effect of the PTEN gene on adhesion, invasion and metastasis of osteosarcoma cells.

    abstract::The phosphatase and tensin homolog (PTEN) gene, an important tumor-suppressor gene, has been demonstrated to have the potential for inhibiting proliferation, migration and invasion in various types of cancer cells. The aim of the present study was to investigate the effect of PTEN expression on osteosarcoma (OS) cells...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3362

    authors: Hu Y,Xu S,Jin W,Yi Q,Wei W

    更新日期:2014-10-01 00:00:00

  • Induction of apoptosis by the angucyclinone antibiotic chemomicin in human tumor cells.

    abstract::Chemomicin (CHM), an angucyclinone antibiotic extracted from the fermentation broth of Nocardia Mediterranei subsp. Kanglensis 1747-64, shows immunosuppressive activity. However, whether it can inhibit growth of tumor cells remains elusive. In the present study, we show that CHM potently inhibited the proliferations o...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Li Y,Han N,Gao N,Xu R,Sun C,Li D,He Q

    更新日期:2010-02-01 00:00:00

  • G-CSF and/or M-CSF accelerate differentiation of bone marrow cells into endothelial progenitor cells in vitro.

    abstract::It has been reported that granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) can mobilize endothelial progenitor cells (EPCs) in bone marrow cells (BMCs) into peripheral blood (PB) in vivo. Previously, we also reported that macrophage-colony stimulating factor (...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Zhang Y,Adachi Y,Iwasaki M,Minamino K,Suzuki Y,Nakano K,Koike Y,Mukaide H,Shigematsu A,Kiriyama N,Li C,Ikehara S

    更新日期:2006-06-01 00:00:00

  • USP14 activation promotes tumor progression in hepatocellular carcinoma.

    abstract::To elucidate the molecular mechanisms underlying the pathogenesis and treatment of human primary hepatocellular carcinoma (HCC), it is important to explore novel HCC-associated genes. In the present study, we examined the expression of ubiquitin-specific peptidase 14 (USP14) in patients with HCC using quantitative PCR...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4296

    authors: Huang G,Li L,Zhou W

    更新日期:2015-12-01 00:00:00

  • sATP‑binding cassette subfamily G member 2 enhances the multidrug resistance properties of human nasal natural killer/T cell lymphoma side population cells.

    abstract::Extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKL) is a rare type of non‑Hodgkin's lymphoma that is associated with limited effective treatment options and unfavorable survival rate, which is partly the result of multidrug resistance (MDR). The presence of side population (SP) cells‑SNK‑6/ADM‑SP (SSP) c...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2020.7722

    authors: Wu S,Zhang X,Dong M,Yang Z,Zhang M,Chen Q

    更新日期:2020-10-01 00:00:00

  • Minimal residual disease monitoring in neuroblastoma patients based on the expression of a set of real-time RT-PCR markers in tumor-initiating cells.

    abstract::Minimal residual disease (MRD) is derived from tumor-initiating cells (TICs) and is responsible for tumor relapse. Neuroblastoma is characterized by extreme tumor heterogeneity, and more than half of high-risk patients experience tumor relapse. To overcome tumor heterogeneity and ac...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2286

    authors: Hartomo TB,Kozaki A,Hasegawa D,Van Huyen Pham T,Yamamoto N,Saitoh A,Ishida T,Kawasaki K,Kosaka Y,Ohashi H,Yamamoto T,Morikawa S,Hirase S,Kubokawa I,Mori T,Yanai T,Hayakawa A,Takeshima Y,Iijima K,Matsuo M,Nishio H

    更新日期:2013-04-01 00:00:00

  • Adenovirus-mediated p53 and ING4 gene co-transfer elicits synergistic antitumor effects through enhancement of p53 acetylation in breast cancer.

    abstract::Multigene-based combination therapy may be an effective practice in cancer gene therapy. Substantial studies have demonstrated that tumor suppressor p53 acetylation is indispensable for p53 activation. Inhibitor of growth 4 (ING4), as a novel tumor suppressor, is capable of remarkably enhancing p53 acetylation and its...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4385

    authors: Wu J,Zhu Y,Xu C,Xu H,Zhou X,Yang J,Xie Y,Tao M

    更新日期:2016-01-01 00:00:00

  • MicroRNA-365 inhibits proliferation, migration and invasion of glioma by targeting PIK3R3.

    abstract::A growing body of evidence suggests that microRNA-365 (miR-365) played crucial role in the initiation and development of many types of cancers. However, the biological role of miR-365 in human glioma remains unclear. Herein, the aims of this study were to investigate the role and underlying mechanisms of miR-365 in gl...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.5458

    authors: Zhu Y,Zhao H,Rao M,Xu S

    更新日期:2017-04-01 00:00:00

  • All-trans retinoic acid upregulates the expression of p53 via Axin and inhibits the proliferation of glioma cells.

    abstract::All-trans retinoic acid (ATRA) is a potent chemopreventive and therapeutic agent and exerts its effects by inducing growth arrest. In the present study, we demonstrated that ATRA activated the expression of p53 via Axin and induced cell cycle arrest at the G1/S phase and apoptosis of glioma cells. Briefly, C6 cells we...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2391

    authors: Lu J,Zhang F,Yuan Y,Ding C,Zhang L,Li Q

    更新日期:2013-06-01 00:00:00

  • Pien Tze Huang induces apoptosis in multidrug‑resistant U2OS/ADM cells via downregulation of Bcl‑2, survivin and P-gp and upregulation of Bax.

    abstract::Pien Tze Huang (PZH) is a well-known traditional Chinese formula that was first prescribed by a royal physician in the Ming Dynasty. PZH has been used to treat various types of cancers including osteosarcoma. Previous studies have shown that PZH may effectively inhibit osteosarcoma cell growth in vivo and in vitro via...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2916

    authors: Zhang Y,Wang Q,Niu S,Liu J,Zhang L

    更新日期:2014-02-01 00:00:00

  • Alteration of gene expression and DNA methylation in drug-resistant gastric cancer.

    abstract::The mechanisms of drug resistance in cancer are not fully elucidated. To study the drug resistance of gastric cancer, we analyzed gene expression and DNA methylation profiles of 5-fluorouracil (5-FU)- and cisplatin (CDDP)-resistant gastric cancer cells and biopsy specimens. Drug-resistant gastric cancer cells were est...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3014

    authors: Maeda O,Ando T,Ohmiya N,Ishiguro K,Watanabe O,Miyahara R,Hibi Y,Nagai T,Yamada K,Goto H

    更新日期:2014-04-01 00:00:00

  • DAL-1 attenuates epithelial to mesenchymal transition and metastasis by suppressing HSPA5 expression in non-small cell lung cancer.

    abstract::Metastasis is the primary cause of death in lung cancer patients and EMT (epithelial-mesenchymal transition) promotes metastasis. Previous study revealed that DAL-1 (differentially expressed in adenocarcinoma of the lung) could attenuate EMT and metastasis in non-small cell lung cancer (NSCLC). Further study proved th...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.6000

    authors: Qiu X,Guan X,Liu W,Zhang Y

    更新日期:2017-11-01 00:00:00

  • Quercetin induces FasL-related apoptosis, in part, through promotion of histone H3 acetylation in human leukemia HL-60 cells.

    abstract::Quercetin, a naturally occurring flavonoid abundant in fruits and vegetables, has been demonstrated as a multipotent bioflavonoid with great potential for the prevention and treatment of cancer. Apoptosis is thought to be an important response to most chemotherapeutic agents in leukemia cells. However, the underlying ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2010.1097

    authors: Lee WJ,Chen YR,Tseng TH

    更新日期:2011-02-01 00:00:00

  • Cancer patients treated with the Banerji protocols utilising homoeopathic medicine: a Best Case Series Program of the National Cancer Institute USA.

    abstract::Although many studies have been conducted on the role of alternative medicine in the treatment of cancer, only a few reports have been published regarding the total regression of malignant tumors. At the PBH Research Foundation (PBHRF), two of the authors have used homoeopathic therapy to treat many patients with vari...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Banerji P,Campbell DR,Banerji P

    更新日期:2008-07-01 00:00:00

  • Non‑invasive monitoring of paclitaxel and lenvatinib efficacy against anaplastic thyroid cancer in orthotopic SCID mouse models using small‑animal FDG‑PET/CT.

    abstract::Anaplastic thyroid carcinoma (ATC) is a rare type of thyroid carcinoma with a poor prognosis. Thus, suitable preclinical tumor models are required for the development of new ATC therapies. In the present study, orthotopic tumor xenograft models were established using ATC cell lines and SCID mice, and tumor invasion an...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2020.7720

    authors: Aoyama M,Takizawa H,Otani T,Inoue S,Kawakita N,Tsuboi M,Bando Y,Uehara H,Kondo K,Tangoku A

    更新日期:2020-10-01 00:00:00