Abstract:
BACKGROUND:Microtubule Targeting Agents (MTAs) including paclitaxel, colchicine and vinca alkaloids are widely used in the treatment of various cancers. As with most chemotherapeutic agents, adverse effects and drug resistance are commonly associated with the clinical use of these agents. Methyl 2-(5-fluoro-2-hydroxyphenyl)-1H- benzo[d]imidazole-5-carboxylate (MBIC), a benzimidazole derivative displays greater toxicity against various cancer compared to normal human cell lines. The present study, focused on the cytotoxic effects of MBIC against HeLa cervical cancer cells and possible actions on the microtubule assembly. METHODS:Apoptosis detection and cell-cycle assays were performed to determine the type of cell death and the phase of cell cycle arrest in HeLa cells. Tubulin polymerization assay and live-cell imaging were performed to visualize effects on the microtubule assembly in the presence of MBIC. Mitotic kinases and mitochondrial-dependent apoptotic proteins were evaluated by Western blot analysis. In addition, the synergistic effect of MBIC with low doses of selected chemotherapeutic actions were examined against the cancer cells. RESULTS:Results from the present study showed that following treatment with MBIC, the HeLa cells went into mitotic arrest comprising of multi-nucleation and unsegregated chromosomes with a prolonged G2-M phase. In addition, the HeLa cells showed signs of mitochondrial-dependant apoptotic features such as the release of cytochrome c and activation of caspases. MBIC markedly interferes with tubulin polymerization. Western blotting results indicated that MBIC affects mitotic regulatory machinery by up-regulating BubR1, Cyclin B1, CDK1 and down-regulation of Aurora B. In addition, MBIC displayed synergistic effect when given in combination with colchicine, nocodazole, paclitaxel and doxorubicin. CONCLUSION:Taken together, our study demonstrated the distinctive microtubule destabilizing effects of MBIC against cervical cancer cells in vitro. Besides that, MBIC exhibited synergistic effects with low doses of selected anticancer drugs and thus, may potentially reduce the toxicity and drug resistance to these agents.
journal_name
J Exp Clin Cancer Resjournal_title
Journal of experimental & clinical cancer research : CRauthors
Hasanpourghadi M,Karthikeyan C,Pandurangan AK,Looi CY,Trivedi P,Kobayashi K,Tanaka K,Wong WF,Mustafa MRdoi
10.1186/s13046-016-0332-0subject
Has Abstractpub_date
2016-03-31 00:00:00pages
58eissn
0392-9078issn
1756-9966pii
10.1186/s13046-016-0332-0journal_volume
35pub_type
杂志文章abstract:BACKGROUND:Antibody Directed Enzyme Prodrug Therapy (ADEPT) can be used to generate cytotoxic agents at the tumor site. To date non-human enzymes have mainly been utilized in ADEPT. However, these non-human enzymes are immunogenic limiting the number of times that ADEPT can be administered. To overcome the problem of i...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-28-147
更新日期:2009-12-03 00:00:00
abstract:BACKGROUND:Development of resistance to therapy continues to be a serious clinical problem in lung cancer management. We previously identified that Annexin A2 is significantly up-regulated in cisplatin-resistant non-small cell lung cancer (NSCLC) A549/DDP cells. However, the exact function and molecular mechanism of An...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-017-0594-1
更新日期:2017-09-08 00:00:00
abstract::Prostate cancer (PC) development reflects a complex sequence of biologic and molecular events. Several inheritable and somatic genetic changes have been identified. The knowledge of the molecular basis of PC can improve our understanding of the causes of this common cancer and provide information on prognosis and trea...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:
更新日期:2007-03-01 00:00:00
abstract::In the field of gut endocrinomas (carcinoids and relevant neoplasms), several classifications have been internationally accepted and utilized at varying frequency. The basis of the concepts regarding gut endocrinomas from which these classifications have been proposed were drawn from the different aspects. These inclu...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:
更新日期:1999-03-01 00:00:00
abstract::We measured the serum level of soluble Fas (sFas) antigen in gastric MALT (mucosa-associated lymphoid tissue) lymphoma patients to investigate immune response of B lymphoma cells in gastric MALT lymphoma. The serum sFas antigen levels in 21 patients with Helicobacter pylori (HP)-positive MALT lymphoma were 4.51+/-0.25...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract::The mutational spectrum of p53 gene and the biological effects of mutant p53 protein vary greatly from one type of tumor to another. To investigate the biological effects of mutant p53 gene in human lung adenocarcinoma, mutant p53 was silenced by RNA interference (RNAi) in cell line Anip973. Then, the effects of mutan...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2006-12-01 00:00:00
abstract::Occult carcinoma cells in peripheral blood of breast cancer (BC) patients is generally associated with poor disease prognosis. Reverse transcriptase-polymerase chain reaction (RT-PCR) is a sensitive method for revealing rare circulating cancer cells. The target mRNA must be carefully chosen, as it must be expressed on...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2005-06-01 00:00:00
abstract:BACKGROUND:New chemotherapic agents and new protocols in oncology have led to an increasing survival rate in patients affected by tumors. However, this increased use has been accompanied by a growth in the incidence of cutaneous side effects and a worsening of patients' quality of life. Appropriate management of skin t...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-31-50
更新日期:2012-05-28 00:00:00
abstract::Arsenic trioxide has shown substantial efficacy in treating patients with relapsed or refractory acute promyelocytic leukemia (APL) as well as solid tumors. Arsenic can act through a considerable number of different pathways including mitochondrial respiration and tubulin formation, affecting growth, blood flow, diffe...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2004-06-01 00:00:00
abstract:BACKGROUND:Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-30-45
更新日期:2011-04-26 00:00:00
abstract:BACKGROUND:Parallel to complex alteration in molecular and cellular events, enrichment of cancer stem cells (CSC) contributes significantly in deliberation and maintenance of cisplatin resistance. Cisplatin mediated CSC enrichment is well established in various cancers, yet the underlying mechanism is largely unknown. ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-017-0636-8
更新日期:2017-11-23 00:00:00
abstract:PURPOSE:The association between striking life events, an important stress and acute anxiety disorder, and the occurrence of primary breast cancer is unclear. The current meta-analysis was designed to assess the relationship between striking life events and primary breast cancer incidence in women. METHODS:Systematic c...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,meta分析
doi:10.1186/1756-9966-32-53
更新日期:2013-08-13 00:00:00
abstract:BACKGROUND:T-cell Acute Lymphoblastic Leukemia (ALL) represents about 10-15 % of pediatric ALL cases. EZH2, one of the components of Polycomb group proteins (PRC2) complex, catalyzes the trimethylation of histone H3 lysine 27 that is associated with transcriptional repression and tumor development. METHODS:We examined...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-015-0191-0
更新日期:2015-08-14 00:00:00
abstract:BACKGROUND:Aberrant expression of Wiskott-Aldrich syndrome protein interacting protein family member 1 (WIPF1) contributes to the invasion and metastasis of several malignancies. However, the role of WIPF1 in human pancreatic ductal adenocarcinoma (PDAC) remains poorly understood. METHODS:Human pancreatic cancer sampl...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0848-6
更新日期:2018-07-24 00:00:00
abstract::Patients with cervical carcinoma (CC) are frequently immunocompromised. Dendritic cells (DCs) are potent antigen-presenting cells. Using multicolor flow cytometry, the percentages of CD11c+ (DC1) and CD123+ (DC2) subsets, were determined in the peripheral blood of 37 patients with cervical carcinoma (CC), 54 patients ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,随机对照试验
doi:10.1186/1756-9966-29-78
更新日期:2010-06-18 00:00:00
abstract::Radiofrequency Thermal Ablation (RFA) of liver tumors is done by percutaneous, laparoscopic and open surgical approach. Selection criteria for percutaneous or open surgical ablation of 65 hepatic lesions are here evaluated in 45 patients treated in a two-years period. Twenty-five patients were males and 20 females, ag...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2003-12-01 00:00:00
abstract:BACKGROUND:The epithelial-mesenchymal transition (EMT) is crucial for metastasis and positively regulated by calcium-related signaling. The melastatin-related transient receptor potential 7 (TRPM7) regulates a non-selective cation channel and promotes cancer metastasis. However, the mechanisms underlying the action of ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1061-y
更新日期:2019-02-28 00:00:00
abstract:BACKGROUND:Dysregulation of transforming growth factor β (TGF-β) signaling and hypoxic microenvironment have respectively been reported to be involved in disease progression in malignancies of prostate. Emerging evidence indicates that downregulation of TGFBR2, a pivotal regulator of TGF-β signaling, may contribute to ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0764-9
更新日期:2018-04-27 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 已发布勘误
doi:10.1186/s13046-019-1338-1
更新日期:2019-08-02 00:00:00
abstract:BACKGROUND:Although significant progress has been made in the treatment of lymphomas, many lymphomas exhibit resistance to cell death, suggesting a defective Fas signaling, which remains poorly understood. We previously reported that cells expressing the K1 protein of human herpesvirus 8 (HHV-8) resist death through th...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-31-69
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abstract:BACKGROUND:Actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1), a long noncoding RNA, is significantly highly expressed and associated with metastasis and poor prognosis in many cancers, including nasopharyngeal carcinoma (NPC). In this study, we aim to identify the role of AFAP1-AS1 acting as an oncogenic ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0918-9
更新日期:2018-10-16 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,已发布勘误
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更新日期:2020-08-24 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-27-67
更新日期:2008-11-12 00:00:00
abstract::The immune system in patients detects and eliminates tumor cells, but tumors still progress persistently. The mechanisms by which tumor cells survive under the pressure of immune surveillance are not fully understood. This review is to present the evidence from clinical studies, showing a significant correlation of cl...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:10.1186/1756-9966-30-12
更新日期:2011-01-21 00:00:00
abstract:BACKGROUND:Long noncoding RNAs (lncRNAs) are considered critical regulators in cancers; however, the clinical significance and mechanisms of MAPKAPK5-AS1 (hereinafter referred to as MK5-AS1) in colorectal cancer (CRC) remain mostly unknown. METHODS:In this study, quantitative real-time PCR (qPCR) and western blotting ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-020-01633-8
更新日期:2020-07-20 00:00:00
abstract::Axillary lymphadenectomy is a very important procedure in the staging of breast cancer patients. However, it is associated with a significant morbidity rate. On the other hand, using early diagnosis we can see a high number of cases where the lymph nodes are negatives. With the intention of avoiding unnecessary axilla...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2002-06-01 00:00:00
abstract::The aim of this study was to investigate serum levels of IL-2, IL-6 and IL-10 in the pretreatment period and to determine if high IL-2, IL-6, IL-10 levels correlate with the outcome in patients with Non-Hodgkin's Lymphoma (NHL) in the post treatment period. Forty-three patients with the diagnosis of aggressive NHL wer...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2004-09-01 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 已发布勘误
doi:10.1186/s13046-019-1422-6
更新日期:2019-10-15 00:00:00
abstract::Our previous studies have demonstrated the significant enzymatic activity of glycogen phosphorylase (GP) in the gastric carcinoma and proliferating cells of particular intestinal metaplasia (IM). This paper reviewed the identification of the GP isoform in the gastrointestinal carcinoma, and the investigation on the ro...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:
更新日期:1999-03-01 00:00:00
abstract:BACKGROUND:The recently identified phenomenon of double-stranded RNA (dsRNA)-mediated gene activation (RNAa) has been studied extensively, as it is present in humans, mice, and Caenorhabditis elegans, suggesting that dsRNA-mediated RNAa is an evolutionarily conserved mechanism. Previous studies have shown that dsP21-32...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0423-y
更新日期:2016-09-17 00:00:00