Abstract:
BACKGROUND:CYP1B1 is recognized as a valuable target for chemotherapy. It catalyzes the bioactivation of naphthoquinone oximes within certain cancer cell lines. However, the expression level of CYP1B1 in melanoma and the functional role regulating the activity of DMAKO-20 as a representative naphthoquinone oxime against skin carcinoma is still unknown. OBJECTIVE:We sought to examine the expression level of CYP1B1 in melanoma and explore the molecular mechanism behind the anticancer effects of DMAKO-20 in melanoma. METHODS:CYP1B1 expression levels in paraffin specimens taken from melanoma patients, and its expression levels in B16/F10 cancer cells were investigated using immunohistochemical staining. The molecular mechanisms behind DMAKO20 activity against melanoma was investigated by using cytotoxicity, cell scratching, apoptotic, and immunoblotting assays. RESULTS:CYP1B1, the P450 isoform was expressed at high levels in melanoma tissues and cultured B16/F10 cells, but was undetectable in normal tissues or fibroblasts. In cell proliferation assays, the shikonin oxime DMAKO-20 exhibited potent and selective antiproliferative effects against B16/F10 melanoma cells and inhibited migration. Several mechanisms for the anticancer effects of DMAKO-20 have been identified in B16/F10 melanoma cells, including apoptosis, upregulation of mitochondrial apoptotic Bax proteins and downregulation of anti-apoptotic Bcl-2. The results from these mechanistic investigations indicated that DMAKO-20 underwent CYP1B1-mediated metabolic activation to activate anticancer metabolites within melanoma cells. CONCLUSION:DMAKO-20 exhibited a selective cytotoxic effect on melanoma cells through CYP1B1-mediated activation. Using DMAKO-20 as a lead compound, further structural optimization may provide new drug entities for the treatments of malignant skin carcinomas.
journal_name
Curr Cancer Drug Targetsjournal_title
Current cancer drug targetsauthors
Cui J,Zhou X,Huang J,Cui J,Chen Jdoi
10.2174/1568009620666201116112937subject
Has Abstractpub_date
2020-11-15 00:00:00eissn
1568-0096issn
1873-5576pii
CCDT-EPUB-111521pub_type
杂志文章abstract::In this early phase of the new era of molecularly targeted patient friendly cancer chemotherapy, there is a need for novel viable anticancer molecular targets. The MDM2 oncoprotein has been validated as a potential target for cancer drug development. MDM2 amplification and/or overexpression occur in a wide variety of ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009053332672
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abstract::Scaffold-based analogs of cinnamic acid benzyl amide (CABA) exhibit pleiotropic effects in cancer cells, and their exact molecular mechanism of action is under investigation. The present study is part of our systemic analysis of interactions of CABA analogs with their molecular targets. These compounds were shown to i...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009614666140821122718
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abstract::NUPR1 is a transcription factor that has attracted great attention because of its various roles in cancer. Several studies were carried out to determine its molecular targets and mechanism of action to develop novel therapies against cancer. Here, we shed light on the role of NUPR1 in different types of cancer. NUPR1 ...
journal_title:Current cancer drug targets
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doi:10.2174/1568009620666200703152523
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abstract::The experimental cytotoxic drug cyclopentenyl cytosine (CPEC) is an analogue of cytidine. Besides its antiviral effect, its potential use in the treatment of cancer has become an important area of research. CPEC is activated by intracellular phosphorylation ultimately forming its metabolite CPEC-TP. CPEC-TP is a non c...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907781386579
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abstract::Gastrointestinal (GI) tumors are among the leading cause of death in cancer patients worldwide. Particularly, gastric cancer (GC) is the third cause of cancer deaths, whereas esophageal neoplasm is the eighth leading most common cancer worldwide and its incidence, especially adenocarcinoma type, is continuously increa...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009617666170208162058
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abstract:BACKGROUND:Current gene therapy vectors such as viral, non-viral, and bacterial vectors, which are used for cancer treatment, but there are certain safety concerns and stability issues of these conventional vectors. Exosomes are the vesicles of size 40-100 nm secreted from multivesicular bodies into the extracellular e...
journal_title:Current cancer drug targets
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doi:10.2174/1568009620666200924154149
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abstract::Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders of hematopoietic progenitors manifest by cytopenias, bleeding, infection, and potential for progression to acute myelogenous leukemia. The wide spectrum of clinical manifestations, including variability in illness severity and potential for ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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abstract::Aberrant expression of the RON receptor tyrosine kinase contributes to breast cancer malignancy. Although clinical trials of RON targeting are underway, the intriguing issue is the diversity of RON expression as evident by cancer cells expressing different variants including oncogenic RON160. The current study determi...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/15680096113139990038
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abstract:BACKGROUND:Intestinal β-glucuronidase enzyme has a significant importance in colorectal carcinogenesis. Specific inhibition of the enzyme helps prevent immune reactivation of the glucuronide- carcinogens, thus protecting the intestine from ROS (Reactive Oxidative Species) mediatedcarcinogenesis. OBJECTIVES:Advancement...
journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
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abstract:BACKGROUND:Approximately one third of Diffuse Large B cell Lymphomas (DLBCL) are refractory or relapse. Novel therapeutic approaches under scrutiny include inhibitors of B-cell receptor (BCR) signaling. Protein kinase CK2 propels survival, proliferation and stress response in solid and hematologic malignancies and prom...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009617666170427110450
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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abstract::The peptidyl prolyl isomerase (Pin1) that induces cis-trans isomerization of the peptide bond involving serine/threonine-proline has recently been shown to regulate the activity of many phosphoproteins including the ones involved in damage response pathways. We investigated Pin1 as a potential target for enhancing the...
journal_title:Current cancer drug targets
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更新日期:2011-03-01 00:00:00
abstract:BACKGROUND:Oncolytic viruses (OVs), which preferentially infect cancer cells and induce host anti-tumor immune responses, have emerged as an effective melanoma therapy. Tanapoxvirus (TANV), which possesses a large genome and causes mild self-limiting disease in humans, is potentially an ideal OV candidate. Interleukin-...
journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2017-01-01 00:00:00
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journal_title:Current cancer drug targets
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更新日期:2020-01-01 00:00:00
abstract::Targeted therapies focus on signaling pathways in cancer cells and other molecular processes involved in oncogenesis. Recent approaches affect the following major groups: the epidermal growth factor receptor (EGFR)-family, angiogenesis, the eicosanoid pathway, the PKC/ Ras/ MAPK pathway, the proteasome and inducers of...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800906777441780
更新日期:2006-06-01 00:00:00
abstract::Selection of treatment options for clinically localized prostate cancer is based on a host of factors including the patient's age, overall health status, potential complications, clinical tumor stage and Gleason score. It is widely acknowledged that androgen independent disease remains the main obstacle to improving t...
journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
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abstract::Bisphosphonates are the standard of care for preventing skeletal morbidity and treating hypercalcemia of malignancy in patients with bone metastases. Zoledronic acid (intravenous; 4 mg monthly) is approved to prevent skeletal-related events (SREs) in patients with bone metastases from several tumor types, and can impr...
journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
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abstract::With increasing incidence of cancer at most of the sites, and growing economic burden and associated psychological and emotional trauma, it is becoming clearer that more efforts are needed for cancer cure. Since most of the chemotherapeutic drugs are non-selective because they are also toxic to the normal cells, new a...
journal_title:Current cancer drug targets
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abstract::Recent publications on the molecular characterization of malignant glioma have had profound impact on the appreciation of tumoral heterogeneity within and between patients. Both these phenomena are implicated in the variability in clinical outcome between patients, as well as the inevitable recurrence of these tumors ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2017-01-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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abstract::The total expression profiles of two medulloblastoma cell lines resistant to the preactivated form of cyclophosphamide (4-hydroperoxycyclophosphamide, 4-HC) were examined using the Affymetrix GeneChip U133A array. Our primary objective was to look for possible genes, other than the well-studied aldehyde dehydrogenases...
journal_title:Current cancer drug targets
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abstract::Prostate cancer is the most frequently diagnosed tumor in industrialized countries. Endocrine therapy, which is based on interference with androgen signaling is only palliative. Drugs used in prostate cancer therapy are luteinizing hormone releasing hormone (LHRH) agonists and antiandrogens. Application of LHRH agonis...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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journal_title:Current cancer drug targets
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abstract::MicroRNAs (miRNAs) are small non-coding RNAs that bind to the 3'untranslated region of target mRNAs and lead to translation repression or mRNA degradation, thus regulating important cell processes. MiRNA deregulation has been identified in virtually all types of cancer, and miRNA profiling has proved useful in cancer ...
journal_title:Current cancer drug targets
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更新日期:2012-09-01 00:00:00
abstract::Exosomes are small vesicles that are secreted by various types of cells, known to mediate signal transduction between cells. During recent years, novel carriers for the delivery of targeted drugs, chemotherapy drugs and RNAs are under development, which is believed to be beneficial for patients. Considering issues of ...
journal_title:Current cancer drug targets
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更新日期:2018-01-01 00:00:00