Abstract C11: The oxidative stress inducer elesclomol requires copper chelation for its anticancer activity

2009 ◽  
Author(s):  
Masazumi Nagai ◽  
Nha Vho ◽  
Elena Kostik ◽  
Suqin He ◽  
Jane Kepros ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Anticancer Activity ◽  
Copper Chelation ◽  
Oxidative Stress Inducer

Copper-dependent ATP7B up-regulation drives the resistance of TMEM16A-overexpressing head-and-neck cancer models to platinum toxicity

2019 ◽  
Vol 476 (24) ◽  
pp. 3705-3719 ◽  
Author(s):  
Avani Vyas ◽  
Umamaheswar Duvvuri ◽  
Kirill Kiselyov
Keyword(s):  
Oxidative Stress ◽  
Head And Neck ◽  
Transcriptional Activation ◽  
Platinum Resistance ◽  
Mrna Levels ◽  
Strong Positive Correlation ◽  
Platinum Compounds ◽  
Copper Chelation ◽  
Novel Approach ◽  
Cancer Models

Platinum-containing drugs such as cisplatin and carboplatin are routinely used for the treatment of many solid tumors including squamous cell carcinoma of the head and neck (SCCHN). However, SCCHN resistance to platinum compounds is well documented. The resistance to platinum has been linked to the activity of divalent transporter ATP7B, which pumps platinum from the cytoplasm into lysosomes, decreasing its concentration in the cytoplasm. Several cancer models show increased expression of ATP7B; however, the reason for such an increase is not known. Here we show a strong positive correlation between mRNA levels of TMEM16A and ATP7B in human SCCHN tumors. TMEM16A overexpression and depletion in SCCHN cell lines caused parallel changes in the ATP7B mRNA levels. The ATP7B increase in TMEM16A-overexpressing cells was reversed by suppression of NADPH oxidase 2 (NOX2), by the antioxidant N-Acetyl-Cysteine (NAC) and by copper chelation using cuprizone and bathocuproine sulphonate (BCS). Pretreatment with either chelator significantly increased cisplatin's sensitivity, particularly in the context of TMEM16A overexpression. We propose that increased oxidative stress in TMEM16A-overexpressing cells liberates the chelated copper in the cytoplasm, leading to the transcriptional activation of ATP7B expression. This, in turn, decreases the efficacy of platinum compounds by promoting their vesicular sequestration. We think that such a new explanation of the mechanism of SCCHN tumors’ platinum resistance identifies novel approach to treating these tumors.

Synthesis and Anticancer Activity of 9-O-Pyrazole Alkyl Substituted Berberine Derivatives

2019 ◽  
Vol 18 (11) ◽  
pp. 1639-1648 ◽  
Author(s):  
Daipeng Xiao ◽  
Fen He ◽  
Dongming Peng ◽  
Min Zou ◽  
Junying Peng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Human Lung Cancer ◽  
Drug Candidate ◽  
Molecular Docking Study ◽  
Protective Function ◽  
Anti Cancer ◽  
Cancer Activity

Background: Berberine (BBR), an isoquinoline plant alkaloid isolated from plants such as Coptis chinensis and Hydrastis canadensis, own multiple pharmacological activities. Objective: In this study, seven BBR derivatives were synthesized and their anticancer activity against HeLa cervical and A549 human lung cancer cell lines were evaluated in vitro. Methods: The anti-cancer activity was measured by MTT assay, and apoptosis was demonstrated by the annexin V-FITC/PI staining assay. The intracellular oxidative stress was investigated through DCFH-DA assay. The molecular docking study was carried out in molecular operating environment (MOE). Results: Compound B3 and B5 showed enhanced anti-cancer activity compared with BBR, the IC50 for compound B3 and B5 were significantly lower than BBR, and compound B3 at the concentration of 64 or 128 µM induced apoptosis in HeLa and A549 cell lines. The reactive oxygen species (ROS) was generated in both cell lines when treated with 100 µM of all the compounds, and compound B3 and B5 induced higher activity in the generation of ROS, while compound B3 exhibited the highest activity, these results are in accordance with the cytotoxicity results, indicating the cytotoxicity were mostly generated from the oxidative stress. In addition, molecular docking analysis showed that compound B3 had the greatest affinity with Hsp90. Upon binding, the protective function of Hsp90 was lost, which might explain its higher cytotoxicity from molecular interaction aspect. Conclusion: All the results demonstrated that compound B3 and B5 showed significantly higher anti-cancer ability than BBR, and compound B3 is a promising anticancer drug candidate.

Potential Anticancer Activity of Caspian Cobra Venom Through Induction of Oxidative Stress in Glioblastoma Cell Line

2018 ◽  
Vol 89 (4) ◽  
pp. 1161-1166 ◽  
Author(s):  
Niloufar Sinaei ◽  
Abbas Zare Mirakabadi ◽  
Behzad Behnam ◽  
Azadeh Aminzadeh ◽  
Somayyeh Karami-Mohajeri
Keyword(s):  
Oxidative Stress ◽  
Anticancer Activity ◽  
Cell Line ◽  
Cobra Venom ◽  
Glioblastoma Cell Line ◽  
Glioblastoma Cell

scholarly journals Paraquat: An Oxidative Stress Inducer

10.5772/32590 ◽  
2012 ◽  
Author(s):  
Ramiro Lascano ◽  
Nacira Munoz ◽  
German Robert ◽  
Marianela Rodriguez ◽  
Mariana Melchiorre ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Stress Inducer

A Novel Cyclic Dinuclear Gold(I) Complex Induces Anticancer Activity via Oxidative Stress-Mediated Intrinsic Apoptotic Pathway in MDA-MB-231 Cancer Cells

2022 ◽  
Author(s):  
Ahmed K. Abogosh ◽  
Meshal Alghanem ◽  
Saeed Ahmad ◽  
Abdullah Alasmari ◽  
Homood M. As Sobeai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Elemental Analysis ◽  
Intrinsic Apoptotic Pathway ◽  
Apoptotic Pathway ◽  
X Ray ◽  
X Ray Crystallography ◽  
Ethyl Amine

A new dinuclear cyclic gold(I) complex [Au2(DCyPA)2](PF6)2, 1 based on bis[2-(dicyclohexylphosphano)ethyl]amine (DCyPA) has been synthesized and characterized by elemental analysis, IR and NMR spectroscopies, and X-ray crystallography. In the dinuclear...

Cadmium as oxidative stress inducer in brain of subacutely exposed rats and its implication on zinc level

2017 ◽  
Vol 280 ◽  
pp. S152
Author(s):  
Zorica Bulat ◽  
Marijana Curcic ◽  
Marko Antunovic ◽  
Slavica Vucinic ◽  
Aleksandra Buha Djordjevic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Zinc Level ◽  
Oxidative Stress Inducer

scholarly journals Cytotoxicity of anticancer aziridinyl-substituted benzoquinones in primary mice splenocytes.

2014 ◽  
Vol 61 (4) ◽  
Author(s):  
Valė Miliukienė ◽  
Henrikas Nivinskas ◽  
Narimantas Čėnas
Keyword(s):  
Oxidative Stress ◽  
Side Effects ◽  
Anticancer Activity ◽  
Anticancer Agent ◽  
Redox Properties ◽  
Primary Cells ◽  
Quinone Oxidoreductase ◽  
Electron Reduction

The anticancer activity of aziridinyl-quinones is mainly attributed to their quinone oxidoreductase 1 (NQO1)-catalyzed two-electron reduction into DNA-alkylating products. However, little is known about their cytotoxicity in primary cells, which may be important in understanding their side effects. We found that the cytotoxicity of aziridinyl-unsubstituted quinones (n = 12) in mice splenocytes with a low amount of NQO1, 4 nmol × mg(-1) × min(-1), was caused mainly by the oxidative stress. Aziridinyl-benzoquinones (n = 6) including a novel anticancer agent RH1 were more cytotoxic than aziridinyl-unsubstituted ones with the similar redox properties, and their cytotoxicity was not decreased by an inhibitor of NQO1, dicumarol. The possible reasons for their enhanced cytotoxicity are discussed.

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