Selective Antitumor Effect of Shikonin Derived DMAKO-20 on Melanoma through CYP1B1.

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.

authors

Cui J,Zhou X,Huang J,Cui J,Chen J

doi

10.2174/1568009620666201116112937

subject

Has Abstract

pub_date

2020-11-15 00:00:00

eissn

1568-0096

issn

1873-5576

pii

CCDT-EPUB-111521

pub_type

杂志文章
  • Small molecule antagonists of the MDM2 oncoprotein as anticancer agents.

    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

    authors: Buolamwini JK,Addo J,Kamath S,Patil S,Mason D,Ores M

    更新日期:2005-02-01 00:00:00

  • Analogs of cinnamic acid benzyl amide as nonclassical inhibitors of activated JAK2 kinase.

    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

    authors: Mielecki M,Milner-Krawczyk M,Grzelak K,Mielecki D,Krzysko KA,Lesyng B,Priebe W

    更新日期:2014-01-01 00:00:00

  • Targeting NUPR1 for Cancer Treatment: A Risky Endeavor.

    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

    pub_type: 杂志文章

    doi:10.2174/1568009620666200703152523

    authors: Mansour SMA,Ali SA,Nofal S,Soror SH

    更新日期:2020-01-01 00:00:00

  • Cyclopentenyl cytosine (CPEC): an overview of its in vitro and in vivo activity.

    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

    authors: Schimmel KJ,Gelderblom H,Guchelaar HJ

    更新日期:2007-08-01 00:00:00

  • The Role of Target Therapy in the Treatment of Gastrointestinal Noncolorectal Cancers: Clinical Impact and Cost Consideration.

    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

    authors: Berretta M,Romano C,Di Francia R,De Diviitis C,Canzonieri V,Caraglia M,Facchini G,Nasti G

    更新日期:2018-01-01 00:00:00

  • Exosome as a Natural Gene Delivery Vector for Cancer Treatment.

    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

    pub_type: 杂志文章

    doi:10.2174/1568009620666200924154149

    authors: Pofali P,Mondal A,Londhe V

    更新日期:2020-01-01 00:00:00

  • Myelodysplastic syndromes: review of pathophysiology and current novel treatment approaches.

    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

    doi:10.2174/156800907781662284

    authors: Warlick ED,Smith BD

    更新日期:2007-09-01 00:00:00

  • Oncogenic variant RON160 expression in breast cancer and its potential as a therapeutic target by small molecule tyrosine kinase inhibitor.

    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

    authors: Yao HP,Zhuang CM,Zhou YQ,Zeng JY,Zhang RW,Wang MH

    更新日期:2013-07-01 00:00:00

  • Advances in In-Silico based Predictive In-Vivo Profiling of Novel Potent β-Glucuronidase Inhibitors.

    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

    pub_type: 杂志文章

    doi:10.2174/1568009619666190320102238

    authors: Yousuf M

    更新日期:2019-01-01 00:00:00

  • A cross-talk between NFAT and NF-κB pathways is crucial for nickel-induced COX-2 expression in Beas-2B cells.

    abstract::Cyclooxygenase-2 (COX-2) is a critical enzyme implicated in chronic inflammation-associated cancer development. Our studies have shown that the exposure of Beas-2B cells, a human bronchial epithelial cell line, to lung carcinogenic nickel compounds results in increased COX-2 expression. However, the signaling pathways...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章

    doi:10.2174/156800911795656001

    authors: Cai T,Li X,Ding J,Luo W,Li J,Huang C

    更新日期:2011-06-01 00:00:00

  • CX-4945, a Selective Inhibitor of Casein Kinase 2, Synergizes with B Cell Receptor Signaling Inhibitors in Inducing Diffuse Large B Cell Lymphoma Cell Death.

    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

    authors: Mandato E,Nunes SC,Zaffino F,Casellato A,Macaccaro P,Tubi LQ,Visentin A,Trentin L,Semenzato G,Piazza F

    更新日期:2018-01-01 00:00:00

  • Chemotherapy Delivery Strategies to the Central Nervous System: neither Optional nor Superfluous.

    abstract::Malignant brain tumors including primary brain tumors (e.g., glioblastoma multiforme) and metastases, are aggressive and lethal entities for the majority of affected patients. Current standard treatments involving combinations of surgery, radiotherapy and systemic chemotherapy offer only modest improvements in surviva...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1568009615666150616123548

    authors: Drapeau A,Fortin D

    更新日期:2015-01-01 00:00:00

  • Peptidyl prolyl isomerase, Pin1 is a potential target for enhancing the therapeutic efficacy of etoposide.

    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

    pub_type: 杂志文章

    doi:10.2174/156800911794519761

    authors: Mathur R,Chandna S,N Kapoor P,S Dwarakanath B

    更新日期:2011-03-01 00:00:00

  • Oncolytic Tanapoxvirus Expressing Interleukin-2 is Capable of Inducing the Regression of Human Melanoma Tumors in the Absence of T Cells.

    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

    pub_type: 杂志文章

    doi:10.2174/1568009617666170630143931

    authors: Zhang T,Kordish DH,Suryawanshi YR,Eversole RR,Kohler S,Mackenzie CD,Essani K

    更新日期:2018-01-01 00:00:00

  • Insight into Discovery of Next Generation Reversible TMLR Inhibitors Targeting EGFR Activating and Drug Resistant T790M Mutants.

    abstract:BACKGROUND:Epidermal growth factor receptor (EGFR) is a well-recognised drug target exploited for treating non-small cell lung cancer (NSCLC). Gefitinib and erlotinib are first generation clinically employed inhibitors used against EGFR activating mutants. However, during course of treatment these inhibitors become ine...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1568009617666170330112842

    authors: Agarwal SM,Pal D,Gupta M,Saini R

    更新日期:2017-01-01 00:00:00

  • Targeting IDH Mutations in AML: Wielding the Double-edged Sword of Differentiation.

    abstract::The genomic characterization of acute myeloid leukemia (AML) by DNA sequencing has illuminated subclasses of the disease, with distinct driver mutations, that might be responsive to targeted therapies. Approximately 15-23% of AML genomes harbor mutations in one of two isoforms of isocitrate dehydrogenase (IDH1 or IDH2...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章

    doi:10.2174/1568009620666200424145622

    authors: Becker JS,Fathi AT

    更新日期:2020-01-01 00:00:00

  • Targeted therapies in non-small cell lung cancer: proven concepts and unfulfilled promises.

    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

    authors: Auberger J,Loeffler-Ragg J,Wurzer W,Hilbe W

    更新日期:2006-06-01 00:00:00

  • Novel targeting of apoptosis pathways for prostate cancer therapy.

    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

    pub_type: 杂志文章,评审

    doi:10.2174/1568009043481623

    authors: Garrison JB,Kyprianou N

    更新日期:2004-02-01 00:00:00

  • Elaborating the Role of Natural Products on the Regulation of Autophagy and their Potentials in Breast Cancer Therapy.

    abstract::Autophagy is an intracellular lysosomal/vacuolar degradation system, in which the inner cytoplasmic cell membrane is degraded by the lysosomal hydrolases, followed by the resulting products released back into the cytosol. It is involved in many physiological processes which are crucial for cell growth and survival. Ho...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1568009617666170330124819

    authors: Zhou X,Yue GG,Tsui SK,Pu J,Fung KP,Lau CB

    更新日期:2018-01-01 00:00:00

  • Bisphosphonates in the prevention of disease recurrence: current results and ongoing trials.

    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

    pub_type: 杂志文章,评审

    doi:10.2174/156800909789760267

    authors: Gnant M

    更新日期:2009-11-01 00:00:00

  • MiRNA153 Reduces Effects of Chemotherapeutic Agents or Small Molecular Kinase Inhibitor in HCC Cells.

    abstract::MicroRNA-153 (miR-153) is considered to be a tumor regulator. Silencing of miR-153 expression induced apoptosis in breast cancer cells. Data on mechanism suggest that up-regulation of miR- 153 level promotes cell proliferation via the down regulation of the expression of PTEN or FOXO1, which attenuates the proliferati...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章

    doi:10.2174/1568009615666150225122635

    authors: Chen Y,Feng F,Gao X,Wang C,Sun H,Zhang C,Zeng Z,Lu Y,An L,Qu J,Wang F,Yang Y

    更新日期:2015-01-01 00:00:00

  • Predictive molecular markers of response to epidermal growth factor receptor(EGFR) family-targeted therapies.

    abstract::Constitutive activation of the EGFR/RAS/PI3K cell-signaling pathway that may occur through molecular aberrations in core pathway components occurs in many solid tumours, including colorectal cancer(CRC), non-small-cell lung cancer(NSCLC) and breast cancer. Predictive biomarkers of response to therapeutics targeting th...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/156800910793357925

    authors: Barton S,Starling N,Swanton C

    更新日期:2010-12-01 00:00:00

  • Transcription factors: molecular targets for prostate cancer intervention by phytochemicals.

    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

    pub_type: 杂志文章,评审

    doi:10.2174/156800907780809732

    authors: Kaur M,Agarwal R

    更新日期:2007-06-01 00:00:00

  • Malignant Glioma In Vitro Models: On the Utilization of Stem-like Cells.

    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

    doi:10.2174/1568009616666160813191809

    authors: Balvers RK,Dirven CM,Leenstra S,Lamfers ML

    更新日期:2017-01-01 00:00:00

  • Cancer vaccines for hormone/growth factor immune deprivation: a feasible approach for cancer treatment.

    abstract::One of the older and most validated cancer treatments is endocrine therapy. Some tumors are dependent on hormone stimulation for growth, and therefore therapeutic interventions aiming to deprive the cells of the hormone are feasible and have been successful. Tumor growth also depends in some cases on growth factors, s...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/156800907780618310

    authors: González G,Lage A

    更新日期:2007-05-01 00:00:00

  • The gene expression profiles of medulloblastoma cell lines resistant to preactivated cyclophosphamide.

    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

    pub_type: 杂志文章

    doi:10.2174/156800908784293631

    authors: Bacolod MD,Lin SM,Johnson SP,Bullock NS,Colvin M,Bigner DD,Friedman HS

    更新日期:2008-05-01 00:00:00

  • Antiandrogens in prostate cancer endocrine therapy.

    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

    doi:10.2174/1568009043332925

    authors: Culig Z,Bartsch G,Hobisch A

    更新日期:2004-08-01 00:00:00

  • Nanoradiopharmaceuticals for Bone Cancer Metastasis Imaging.

    abstract::Drug delivery systems are under intense investigation all around the world, especially in oncology research. Indeed, in some cases, like bone metastasis, nanodrugs may represent the last and best choice for both treatment and imaging of early cancer foci. Nuclear medicine has been using MDP labelled with 99mTc as radi...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章

    doi:10.2174/1568009615666150407125020

    authors: Coelho BF,de Souza Albernaz M,Iscaife A,Moreira Leite KR,de Souza Junqueira M,Bernardes ES,da Silva EO,Santos-Oliveira R

    更新日期:2015-01-01 00:00:00

  • MicroRNAs in the pathobiology of multiple myeloma.

    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

    pub_type: 杂志文章,评审

    doi:10.2174/156800912802429274

    authors: Lionetti M,Agnelli L,Lombardi L,Tassone P,Neri A

    更新日期:2012-09-01 00:00:00

  • Cell-derived Exosomes as Promising Carriers for Drug Delivery and Targeted Therapy.

    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

    pub_type: 杂志文章,评审

    doi:10.2174/1568009617666170710120311

    authors: Wang X,Zhang H,Yang H,Bai M,Ning T,Li S,Li J,Deng T,Ying G,Ba Y

    更新日期:2018-01-01 00:00:00