Platinum complexes as light promoted anticancer agents: a redefined strategy for controlled activation

2016 ◽  
Vol 45 (48) ◽  
pp. 19157-19171 ◽  
Author(s):  
Koushambi Mitra
Keyword(s):  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Light Exposure ◽  
Reactive Oxygen ◽  
Platinum Complexes ◽  
Oxygen Species

Platinum complexes can act as prodrugs which are non-cytotoxic in the dark but generate active platinum(ii) species and lethal reactive oxygen species on light exposure only in cancer cells, therefore leaving healthy cells unaffected.

Oridonin induces oxidative stress-mediated cancer cells apoptosis via targeting thioredoxin reductase

2021 ◽  
Vol 23 ◽  
Author(s):  
Dongzhu Duan ◽  
Xiaolu Feng ◽  
Dabo Pan ◽  
Le Wang ◽  
Yanru Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Malignant Tumors ◽  
Thioredoxin Reductase ◽  
Reactive Oxygen ◽  
Annexin V ◽  
Oxygen Species ◽  
Reduction Assay

Background: Thioredoxin reductase (TrxR) plays vital role in regulating cellular redox balance as well as redox-mediated signal transduction. Accumulating evidence supports that overactivation of TrxR is closely related to tumorigenesis and that targeting TrxR ablation reverses the growth of numerous malignant tumors, making TrxR a promising target for cancer chemotherapy. Thus, the discovery and development of molecules as promising anticancer agents that target TrxR is of great significance. Oridonin was shown to inhibit TrxR activity, but the detailed cellular mechanism is largely unknown. Objective: The study investigated the mechanism of action and underlying inhibitory properties of oridonin on TrxR in HeLa cells. Methods: A covalent docking was performed to reveal the possible interaction between oridonin and TrxR by Schrödinger Software Suite. TrxR activity was determined by 5,5’-dithiobis-2-nitrobenzoic acid reduction assay and endpoint insulin reduction assay. Sulforhodamine B and colony formation assay were employed to assess the viability and growth of cells. Reactive oxygen species level was measured by probe 2’, 7’-dichlorfluorescein diacetate, and dihydroethidium. Hoechst 33342 staining, caspase 3 activation, and fluorescein-5-isothiocyanate-conjugated Annexin V and propidium iodide double staining were used to evaluate apoptosis. Results: Here, we reported the oridonin as a potent inhibitor of TrxR. Inhibition of TrxR results in a decrease of thiols content and total glutathione elevates reactive oxygen species levels, and finally promotes oxidative stress-mediated apoptosis of cancer cells. Conclusion : Targeting TrxR by oridonin discloses a novel molecular mechanism underlying the biological action of oridonin and sheds light on developing oridonin as a potential tumor therapeutic agent.

Small-molecule anticancer agents kill cancer cells by harnessing reactive oxygen species in an iron-dependent manner

2018 ◽  
Vol 16 (9) ◽  
pp. 1465-1479 ◽  
Author(s):  
Sara R. Fedorka ◽  
Kevin So ◽  
Ayad A. Al-Hamashi ◽  
Ibtissam Gad ◽  
Ronit Shah ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Cell Lines ◽  
Small Molecule ◽  
Anticancer Agents ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Open Chain ◽  
New Class

In the course of generating a library of open-chain epothilones, we discovered a new class of small molecule anticancer agents that has no effect on tubulin but instead kills selected cancer cell lines by harnessing reactive oxygen species in an iron-dependent manner.

Reserpine Induces Apoptosis and Cell Cycle Arrest in Hormone Independent Prostate Cancer Cells through Mitochondrial Membrane Potential Failure

2019 ◽  
Vol 18 (9) ◽  
pp. 1313-1322 ◽  
Author(s):  
Manjula Devi Ramamoorthy ◽  
Ashok Kumar ◽  
Mahesh Ayyavu ◽  
Kannan Narayanan Dhiraviam
Keyword(s):  
Prostate Cancer ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Membrane Potential ◽  
Cancer Cells ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Prostate Cancer Cells

Background: Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism of its anti-cancer activity on hormonal independent prostate cancer remains elusive. Methods: we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species (ROS) and cell cycle analysis. Results: Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential, reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results. Conclusion: Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment of androgen-independent prostate cancer.

scholarly journals Photo-Responsive Supramolecular Micelles for Controlled Drug Release and Improved Chemotherapy

2020 ◽  
Vol 22 (1) ◽  
pp. 154
Author(s):  
Fasih Bintang Ilhami ◽  
Kai-Chen Peng ◽  
Yi-Shiuan Chang ◽  
Yihalem Abebe Alemayehu ◽  
Hsieh-Chih Tsai ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Drug Release ◽  
Visible Light ◽  
Cancer Cells ◽  
Laser Irradiation ◽  
Reactive Oxygen ◽  
Controlled Drug Release ◽  
Grand Challenge ◽  
Supramolecular System ◽  
Oxygen Species

Development of stimuli-responsive supramolecular micelles that enable high levels of well-controlled drug release in cancer cells remains a grand challenge. Here, we encapsulated the antitumor drug doxorubicin (DOX) and pro-photosensitizer 5-aminolevulinic acid (5-ALA) within adenine-functionalized supramolecular micelles (A-PPG), in order to achieve effective drug delivery combined with photo-chemotherapy. The resulting DOX/5-ALA-loaded micelles exhibited excellent light and pH-responsive behavior in aqueous solution and high drug-entrapment stability in serum-rich media. A short duration (1–2 min) of laser irradiation with visible light induced the dissociation of the DOX/5-ALA complexes within the micelles, which disrupted micellular stability and resulted in rapid, immediate release of the physically entrapped drug from the micelles. In addition, in vitro assays of cellular reactive oxygen species generation and cellular internalization confirmed the drug-loaded micelles exhibited significantly enhanced cellular uptake after visible light irradiation, and that the light-triggered disassembly of micellar structures rapidly increased the production of reactive oxygen species within the cells. Importantly, flow cytometric analysis demonstrated that laser irradiation of cancer cells incubated with DOX/5-ALA-loaded A-PPG micelles effectively induced apoptotic cell death via endocytosis. Thus, this newly developed supramolecular system may offer a potential route towards improving the efficacy of synergistic chemotherapeutic approaches for cancer.

A 60-Hz sinusoidal magnetic field induces apoptosis of prostate cancer cells through reactive oxygen species

2008 ◽  
Vol 84 (11) ◽  
pp. 945-955 ◽  
Author(s):  
Eui Kwan Koh ◽  
Byung-Kyu Ryu ◽  
Dong-Young Jeong ◽  
Iel-Soo Bang ◽  
Myung Hee Nam ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Prostate Cancer ◽  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Prostate Cancer Cells ◽  
Sinusoidal Magnetic Field
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