Abstract:
BACKGROUND:Osteosarcoma (OS) is a malignant tumor of the bone mostly observed in children and adolescents. The current treatment approach includes neoadjuvant and adjuvant chemotherapy; however, drug resistance often hinders therapy in OS patients. Also, the post-relapse survival of OS patients is as low as 20%. We therefore planned to understand the molecular cause for its poor prognosis and design an appropriate therapeutic strategy to combat the disease. METHODS:We analyzed OS patient dataset from Gene Expression Omnibus (GEO) and identified the differentially expressed genes and the top deregulated pathways in OS. Subsequently, drugs targeting the major de-regulated pathways were selected and the following assays were conducted- MTT assay to assess cytotoxicity of drugs in OS cells; immunoblotting and immunostaining to analyze key protein expression and localization after drug treatment; LysoTracker staining to monitor lysosomes; Acridine Orange to label acidic vesicles; and DCFDA to measure Reactive Oxygen Species (ROS). RESULTS:The differential gene expression analysis from OS patient dataset implicated the striking involvement of cellular processes linked to autophagy and protein processing in the development of OS. We therefore selected the FDA approved drugs, chloroquine (CQ) and verteporfin (VP) known for autophagy inhibitory and proteotoxic functions to explore against OS. Importantly, VP, but not CQ, showed an extensive dose-dependent cytotoxicity. It resulted in autophagy disruption at multiple steps extending from perturbation of early autophagic processes, inhibition of autophagic flux to induction of lysosomal instability. Interestingly, VP treated protein lysates showed a ROS-dependent high molecular weight (HMW) band when probed for P62 and P53 protein. Further, VP triggered accumulation of ubiquitinated proteins as well. Since VP had a pronounced disruptive effect on cellular protein homeostasis, we explored the possibility of simultaneous inhibition of the ubiquitin-proteasomal system (UPS) by MG-132 (MG). Addition of a proteasomal inhibitor significantly aggravated VP induced cytotoxicity. MG co-treatment also led to selective targeting of P53 to the lysosomes. CONCLUSION:Herein, we propose VP and MG induce regulation of autophagy and protein homeostasis which can be exploited as an effective therapeutic strategy against osteosarcoma.
journal_name
Cancer Cell Intjournal_title
Cancer cell internationalauthors
Saini H,Sharma H,Mukherjee S,Chowdhury S,Chowdhury Rdoi
10.1186/s12935-020-01720-ysubject
Has Abstractpub_date
2021-01-14 00:00:00pages
52issue
1issn
1475-2867pii
10.1186/s12935-020-01720-yjournal_volume
21pub_type
杂志文章abstract:Background:Nuclear transcription factor kappa B (NF-κB) subunits exhibit crucial roles in tumorigenesis and chemo-sensitivity. Recent studies suggest that RelB, the key subunit of the alternative NF-κB pathway, plays a critical role in the progression of diverse human malignancies. However, the significance of RelB in ...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-018-0677-x
更新日期:2018-11-13 00:00:00
abstract:Background:The crucial role of long non-coding RNAs (lncRNAs) has been certified in human cancers. The lncRNAs with abnormal expressions could act as tumor inhibitors or oncogenes in the advancement of tumors. LBX2-AS1 was once reported to accelerate esophageal squamous cell carcinoma. Nonetheless, its function in gast...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01207-w
更新日期:2020-04-26 00:00:00
abstract:BACKGROUND:Although recent studies have shown the utility of miR-203 as a cancer-relevant biomarker, the validated clinical significance of miR-203 in HCC remains obscure. The aim of the present study was to evaluate the relationship between miR-203 expression and clinicopathological features in HCC patients. METHODS:...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-015-0214-0
更新日期:2015-06-18 00:00:00
abstract::Osteosarcoma (OS) is one of the most prevalent malignant cancers with lower survival and poor overall prognosis mainly in children and adolescents. Identifying the molecular mechanisms and OS stem cells (OSCs) as new concepts involved in disease pathogenesis and progression may potentially lead to new therapeutic targ...
journal_title:Cancer cell international
pub_type: 杂志文章,评审
doi:10.1186/s12935-018-0654-4
更新日期:2018-10-16 00:00:00
abstract:BACKGROUND:Natural killer (NK) cells eliminate virus-infected and tumor cells through the release of perforins and granzymes; they also produce Interferon gamma (IFN-γ) and Tumor necrosis factor alpha (TNF-α), which induce apoptosis in target cells. Many tumors express Heme oxygenase 1 (HO-1), and this expression has b...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-014-0100-1
更新日期:2014-10-01 00:00:00
abstract:Objective:This study aimed to investigate the relationship among miR-145-5p, ANGPT2 and the NOD_LIKE_RECEPTOR pathway, thereby revealing the molecular mechanism of these three factors underlying the proliferation, migration and invasion of gastric cancer (GC) epithelial cells. Methods:qRT-PCR was carried out to detect...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01483-6
更新日期:2020-08-28 00:00:00
abstract:Background:Inflammation is one of a main reason for colon cancer progression and poor prognosis. The high-mobility group box-1 (HMGB1) and glutathione peroxidase 4 (GPX4) are responsible for inflammation, but the relationship between HMGB1 and GPX4 remains unknown about inflammation in colon cancer. Methods:RT-qPCR wa...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01289-6
更新日期:2020-05-29 00:00:00
abstract:Background:Melanoma as a type of skin cancer, is associated with a high mortality rate. Therefore, early diagnosis and efficient surgical treatment of this disease is very important. Photodynamic therapy (PDT) involves the activation of a photosensitizer by light at specific wavelength that interacts with oxygen and cr...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01616-x
更新日期:2020-10-29 00:00:00
abstract:BACKGROUND:The present study mainly aimed to investigate the direct effects of Endostar (ES) on the proliferation and radiosensitivity of human lung squamous cancer cell line H-520. RESULTS:ES significantly inhibited H-520 cell proliferation in a time- and dose-dependent manner. According to the colony-forming assays,...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/1475-2867-10-17
更新日期:2010-05-24 00:00:00
abstract:OBJECTIVES:Bladder transitional cell carcinoma (TCC) is one of the most common solid malignancies in China. This study examined the antitumor effect and underlying mechanism of action of sunitinib malate in human bladder TCC in vitro. METHODS:Bladder TCC cell lines 5637 and BIU87 were maintained in 1640 medium and T24...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-015-0179-z
更新日期:2015-02-28 00:00:00
abstract:Background:Endometrial carcinoma (EC) is one of the three major malignant tumors of the female reproductive system. In recent years, the incidence and mortality rate of EC have increased. B-cell translocation gene 1 (BTG1) is an anti-proliferation gene that regulates the occurrence and development of a variety of tumor...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01591-3
更新日期:2020-10-07 00:00:00
abstract:BACKGROUND:Endometrial cancer is an invasive gynecological cancer prevalent in the world. The pathogenesis of endometrial cancer is related to multiple levels of regulation, referring to oestrogen, tumor-suppressor gene (e.g. PTEN) or microRNAs (e.g. miR-23a and miR-29b). Metapristone is a hormone-related drug, which i...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01682-1
更新日期:2021-01-07 00:00:00
abstract:OBJECTIVE:To explore the relationship between tumor necrosis factor receptor-associated factor 6 (TRAF6) and the clinicopathological features in HCC as well as its biological function. METHODS:Totally, 412 liver tissues were collected, including 171 hepatocellular carcinoma (HCC) and their corresponding non-tumor tiss...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-016-0352-z
更新日期:2016-09-29 00:00:00
abstract:Background:Melanoma is the most aggressive type of skin cancer with high mortality rate and poor prognosis. lncRNA MEG3, a tumor suppressor, is closely related to the development of various cancers. However, the role of lncRNA MEG3 in melanoma has seldom been studied. Methods:RT-PCR was used to examine the expressions...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-019-1087-4
更新日期:2020-01-10 00:00:00
abstract:BACKGROUND:CircRNAs play crucial roles in multiple tumours. However, the functions of most circRNAs in cervical cancer remain unclear. METHODS:This study collected GSE113696 data from the GEO database to search for differentially expressed circRNAs in cervical cancer. Quantitative reverse transcription PCR was used to...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01736-4
更新日期:2021-01-07 00:00:00
abstract:BACKGROUND:Serum Deprivation Protein Response (SDPR) plays an important role in formation of pulmonary alveoli. However, the functions and values of SDPR in lung cancer remain unknown. We explored prognostic value, expression pattern, and biological function of SDPR in non-small cell lung cancer (NSCLC) and KRAS-mutant...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-021-01756-8
更新日期:2021-01-12 00:00:00
abstract:Background:Sarcomas are malignant heterogeneous tumors of mesenchymal derivation. Dedifferentiated liposarcoma (DDLPS) is aggressive with recurrence in 80% and metastasis in 20% of patients. We previously found that miR-133a was significantly underexpressed in liposarcoma tissues. As this miRNA has recently been shown ...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-018-0583-2
更新日期:2018-06-26 00:00:00
abstract:BACKGROUND:Hepatocellular carcinoma is a common cancer, ranking third in cancer-associated deaths. An important cause of cancer patients' mortality is metastasis. At the start of metastasis progression, there is an epithelial-mesenchymal transition, characterized by matrix degradation, junction reductions and vessels f...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-016-0370-x
更新日期:2017-01-04 00:00:00
abstract:Background:Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent malignancies and a major cause of cancer related death worldwide, especially in China. Cell lines are widely used disease models for basic medical research, however, well characterized ESCC cell models from China were seldom reported. Mis...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01268-x
更新日期:2020-05-24 00:00:00
abstract::Application of novel methods in cancer therapy is important in terms of management and treatment of the life-threatening disorder. It appears that autophagy is a potential target in cancer therapy, as a variety of drugs targeting autophagy have shown great potential in reducing the viability and proliferation of cance...
journal_title:Cancer cell international
pub_type: 杂志文章,评审
doi:10.1186/s12935-020-01634-9
更新日期:2020-11-04 00:00:00
abstract:Background:Estrogen sulfotransferase catalyzes conjugation of sulfuryl-group to estradiol/estrone and regulates E2 availability/activity via estrogen-receptor or non-receptor mediated pathways. Sulfoconjugated estrogen fails to bind estrogen-receptor (ER). High estrogen is a known carcinogen in postmenopausal women. Re...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-1153-y
更新日期:2020-03-04 00:00:00
abstract:BACKGROUND:Several reports have revealed that cancer stem cells (CSCs) exist in many types of solid tumors. Some studies have demonstrated that side population (SP) cells isolated from diverse cancer lines harbor cancer stem-like properties, but there are few reports examining the characteristic of SP cells in human ce...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/1475-2867-14-3
更新日期:2014-01-13 00:00:00
abstract:BACKGROUND:In past few years, long non-coding RNAs (lncRNAs) have been reported to play regulatory roles during cancer progression. LncRNA SNHG10 has been explored in several sorts of cancers. However, its detailed role and mechanism are still not well understood in glioma. METHODS:Expression levels of genes were eval...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01649-2
更新日期:2020-12-09 00:00:00
abstract:BACKGROUND:Cyclooxygenase (COX) is a rate-limiting enzyme in prostaglandins synthesis which exists in two isoforms, COX-1 and COX-2. Over-expression of COX-2 was considered to increase the proliferation and enhance the invasiveness of breast cancer cells. It was suggested that genetic variations in COX-2 could influenc...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/1475-2867-14-38
更新日期:2014-05-06 00:00:00
abstract:BACKGROUND:Drug resistance is a major obstacle to successful chemotherapy for epithelial ovarian cancer (EOC). We found a subset of miRNAs associated with the response to first-line platinum-based chemotherapy in EOC by microarray, and miR-206 was one of the most significant miRNAs. The purposes of this study were to e...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01623-y
更新日期:2020-11-03 00:00:00
abstract:Background:Increasing evidences have underlined the importance of long non-coding RNAs (lncRNAs) in human malignancies. LINC00958 has been found involved in some cancers. However, the underlying mechanical performance of LINC00958 in lung adenocarcinoma (LAD) has not been explored yet. Methods:The expression of releva...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-1099-0
更新日期:2020-01-23 00:00:00
abstract:Background:Drug resistance to 5-fluorouracil (5-FU) and recurrence after chemotherapy in colorectal cancer remain a challenge to be resolved for the improvement of patient outcomes. It is recognized that a variety of secretory proteins released from the tumor cells exposed to chemo-drugs into the tumor microenvironment...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01541-z
更新日期:2020-09-14 00:00:00
abstract::Cancer is a major public health problem as one of the leading causes of death worldwide. Deciphering the molecular regulation mechanisms of tumor progression can make way for tumor diagnosis and therapy. Paternally expressed gene 10 (PEG10), located on human chromosome 7q21.3, has turned out to be an oncogene implicat...
journal_title:Cancer cell international
pub_type: 杂志文章,评审
doi:10.1186/s12935-018-0610-3
更新日期:2018-08-13 00:00:00
abstract:Background:Abnormal expressions of long noncoding RNAs (lncRNAs) are very common in clear cell renal cell carcinoma (ccRCC), and some of these have been reported to be highly correlated with prognosis of ccRCC patients. Methods:"edgeR" AND "DEseq" R packages were used to explore differentially expressed genes (DEGs) b...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-019-0928-5
更新日期:2019-08-05 00:00:00
abstract:Background:Breast cancer is the leading cause of oncological mortality among women. Efficient detection of cancer cells in an early stage and potent therapeutic agents targeting metastatic tumors are highly needed to improve survival rates. Emerging evidence indicates that lncRNAs (long noncoding RNAs) are critical reg...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-018-0638-4
更新日期:2018-09-18 00:00:00