A small molecule that induces reactive oxygen species via cellular glutathione depletion

2014 ◽  
Vol 463 (1) ◽  
pp. 53-63 ◽  
Author(s):  
Tatsuro Kawamura ◽  
Yasumitsu Kondoh ◽  
Makoto Muroi ◽  
Makoto Kawatani ◽  
Hiroyuki Osada
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Lines ◽  
Cancer Cell ◽  
Small Molecule ◽  
Reactive Oxygen ◽  
Cancer Cell Lines ◽  
Glutathione Depletion ◽  
Oxygen Species ◽  
Chemical Library ◽  
Cytotoxic Compound

A new cytotoxic compound was found in our chemical library. We revealed that the compound induced reactive oxygen species through glutathione depletion. Moreover, the compound was effective against several cancer cell lines including those harbouring KRAS.

scholarly journals Snake venom causes apoptosis by increasing the reactive oxygen species in colorectal and breast cancer cell lines

2016 ◽  
Vol Volume 9 ◽  
pp. 6485-6498 ◽  
Author(s):  
Abdulrahman Al-Asmari ◽  
Riyasdeen Anvarbatcha ◽  
Mohammad Al-Shahrani ◽  
Mozaffarul Islam
Keyword(s):  
Breast Cancer ◽  
Reactive Oxygen Species ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Snake Venom ◽  
Reactive Oxygen ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Oxygen Species

scholarly journals Dichloroacetate and PX-478 exhibit strong synergistic effects in a various number of cancer cell lines

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jonas Parczyk ◽  
Jérôme Ruhnau ◽  
Carsten Pelz ◽  
Max Schilling ◽  
Hao Wu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Lines ◽  
Cancer Cell ◽  
Synergistic Effects ◽  
Reactive Oxygen ◽  
Cancer Cell Lines ◽  
Tumor Metabolism ◽  
Pyruvate Dehydrogenase Kinase ◽  
Oxygen Species ◽  
Combination Drug

Abstract Background One key approach for anticancer therapy is drug combination. Drug combinations can help reduce doses and thereby decrease side effects. Furthermore, the likelihood of drug resistance is reduced. Distinct alterations in tumor metabolism have been described in past decades, but metabolism has yet to be targeted in clinical cancer therapy. Recently, we found evidence for synergism between dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor, and the HIF-1α inhibitor PX-478. In this study, we aimed to analyse this synergism in cell lines of different cancer types and to identify the underlying biochemical mechanisms. Methods The dose-dependent antiproliferative effects of the single drugs and their combination were assessed using SRB assays. FACS, Western blot and HPLC analyses were performed to investigate changes in reactive oxygen species levels, apoptosis and the cell cycle. Additionally, real-time metabolic analyses (Seahorse) were performed with DCA-treated MCF-7 cells. Results The combination of DCA and PX-478 produced synergistic effects in all eight cancer cell lines tested, including colorectal, lung, breast, cervical, liver and brain cancer. Reactive oxygen species generation and apoptosis played important roles in this synergism. Furthermore, cell proliferation was inhibited by the combination treatment. Conclusions Here, we found that these tumor metabolism-targeting compounds exhibited a potent synergism across all tested cancer cell lines. Thus, we highly recommend the combination of these two compounds for progression to in vivo translational and clinical trials.

scholarly journals Autophagy inhibition enhances Matrine derivative MASM induced apoptosis in cancer cells via a mechanism involving reactive oxygen species-mediated PI3K/Akt/mTOR and Erk/p38 signaling

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuming Zou ◽  
Melika Sarem ◽  
Shengnan Xiang ◽  
Honggang Hu ◽  
Weidong Xu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Reactive Oxygen ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Oxygen Species ◽  
Induced Apoptosis

Abstract Background In the quest for new anti-cancer drugs, the drug discovery process has shifted to screening of active ingredients in traditional eastern medicine. Matrine is an active alkaloid isolated from plants of the Sophora genus used in traditional Chinese herbal medicine that exhibits a wide spectrum of biological properties and has a potential as an anti-proliferative agent. In this study, we investigated the anticancer property of MASM, ([(6aS, 10S, 11aR, 11bR, 11cS)210-Methylamino-dodecahydro-3a, 7a-diaza-benzo (de)anthracene-8-thione]), a potent derivative of matrine. Methods Four epithelial cancer cell lines representing the dominant cancers, namely: A549 (non-small-cell lung cancer cell line), MCF-7 and MDA-MB-231 (breast cancer cell lines), and Hela (cervical cancer cell line) were employed, and the mechanistic underpinning of MASM-induced apoptosis was investigated using flow cytometry, western blot and immunofluorescence. Results MASM, induced apoptosis via caspase 3 dependent and independent pathways, and autophagy in all the four cancer cell lines, but post-EMT (epithelial mesenchymal transition) cells showed greater sensitivity to MASM. Scavenging reactive oxygen species using N-acetylcysteine rescued all cancer cell lines from apoptosis and autophagy. Mechanistic analysis revealed that MASM induced autophagy involves inhibition of Akt signaling and the activation of Erk and p38 signaling, and inhibition of autophagy further enhanced the apoptosis induced by MASM. Conclusions These results indicate that MASM possesses potency against cancer cells and modulating autophagy during MASM administration could be used to further enhance its therapeutic effects.

scholarly journals Dichloroacetate and PX-478 Exhibit Strong Synergistic Effects in a Various Number of Cancer Cell Lines.

2020 ◽  
Author(s):  
Jonas Parczyk ◽  
Jérôme Ruhnau ◽  
Carsten Pelz ◽  
Max Schilling ◽  
Hao Wu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Metabolism ◽  
Synergistic Effects ◽  
Reactive Oxygen ◽  
Cancer Cell Lines ◽  
Pyruvate Dehydrogenase Kinase ◽  
Oxygen Species ◽  
Combination Drug

Abstract Background: One key approach for anticancer therapy is drug combination. Drug combinations can help reduce doses and thereby decrease side effects. Further, the likelihood of drug resistance is reduced. Distinct alterations in tumour metabolism have been described in past decades, but metabolism has yet to be targeted in clinical cancer therapy. Recently, we found evidence for a synergism between dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor and HIF1-α inhibitor PX-478. In this study, we aimed to analyse this synergism in cell lines of different cancer types and to identify the underlying biochemical mechanisms.Methods: The dose-dependent antiproliferative effects of the single drugs and their combination were assessed using MTT or SRB assays. FACS, Western blot and HPLC analyses were performed to investigate changes in reactive oxygen species levels, apoptosis and the cell cycle. Additionally, real-time metabolic analyses (Seahorse) were performed with DCA-treated MCF-7 cells.Results: The combination of DCA and PX-478 produced synergistic effects in all eight cancer cell lines tested, including colorectal, lung, breast, cervical, liver and brain cancer. Reactive oxygen species generation and apoptosis played important roles in this synergism. Furthermore, cell proliferation was inhibited by the combination treatment.Conclusions: Here, we found that these cancer metabolism-targeting compounds exhibited potent synergism across all tested cancer cell lines. Thus, we highly recommend the combination of these two compounds for progression to in vivo translational and clinical trials.

scholarly journals Scorpion Venom Causes Apoptosis by Increasing Reactive Oxygen Species and Cell Cycle Arrest in MDA-MB-231 and HCT-8 Cancer Cell Lines

2018 ◽  
Vol 23 ◽  
pp. 215658721775179 ◽  
Author(s):  
Abdulrahman Khazim Al-Asmari ◽  
Anvarbatcha Riyasdeen ◽  
Mozaffarul Islam
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cancer Cell ◽  
Reactive Oxygen ◽  
Scorpion Venom ◽  
Oxygen Species ◽  
Scorpion Venoms ◽  
Cycle Arrest

Objectives. The objective of this study was to examine the effect of scorpion venoms on cancer cell progression, apoptosis, and cell cycle arrest. Scorpion venoms are known to possess numerous bioactive compounds that act against cancer progression by inducing apoptosis. In this study, we have taken the venoms from the following 2 species of scorpion— Androctonus crassicauda and Leiurus quinquestriatus—and tested the anticancer properties of the venom against breast and colorectal cancer cell lines. Methods. Milking of scorpion venom and culturing the breast and colorectal cancer cell lines were done according to the standard procedure. The venom cytotoxicity was assessed by MTT methods, and the cellular and nuclear changes were studied with phase contrast and propidium iodide staining, respectively. The cell cycle arrest and accumulation of reactive oxygen species were analyzed on a Muse cell analyzer. Results. The venoms exerted cytotoxic effects on breast and colorectal cell lines in a dose- and time-dependent manner. Enhanced apoptotic cells, increase in reactive oxygen species, and cell cycle arrest were observed after challenging these cell lines with scorpion venoms. Conclusions. Scorpion venom induces apoptosis in breast and colorectal cell lines as reflected by the changes in the cell morphology and cell cycle studies. Furthermore, a high percentage of total reactive oxygen species as well as apoptotic cells also contribute to cell death as observed after venom treatments. To the best of authors’ knowledge, this is the first scientific evidence demonstrating the induction of apoptosis and cell cycle arrest by these species of scorpion venoms.

Promotion of Ferroptosis in Oral Cancer Cell Lines by Chrysophanol

2019 ◽  
Vol 18 (3) ◽  
pp. 273-276
Author(s):  
Lin Ya-Hsuan ◽  
Chiu Valeria ◽  
Huang Chun-Yen ◽  
Tzeng I-Shiang ◽  
Hsieh Po-Chun ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Oral Cancer ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Cancer Cell ◽  
Squamous Cell ◽  
Reactive Oxygen ◽  
Oxygen Species

Oral cancer is a type of head and neck cancer that can be life threatening if not diagnosed and treated early. Ferroptosis is a type of programmed or regulated cell death dependent on iron and reactive oxygen species but is a caspase-independent form of non-apoptotic cell death. Therefore, there is a need to identify candidate natural compound that may attenuate carcinogenesis through ferroptosis. To this end, we determined the pharmacological effects of chrysophanol on ferroptosis in two different oral cancer cell lines—FaDu, a hypopharyngeal squamous cell carcinoma and SAS, a poorly differentiated squamous cell carcinoma cell line from human tongue primary lesion. Results indicated that chrysophanol caused overproduction of lipid reactive oxygen species, decreased the level of glutathione peroxidase 4, and increased the level of lipocalin-2 and CCAAT-enhancer-binding protein homologous protein. These findings suggest that chrysophanol has the therapeutic potential to alleviate the progression of oral carcinogenesis through activation of ferroptosis.

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