Curcuminoid WZ26, a TrxR1 inhibitor, effectively inhibits colon cancer cell growth and enhances cisplatin-induced cell death through the induction of ROS

Zhang, Tingting; Zheng, Peisen; Shen, Xin; Shao, Rongrong; Wang, Bin; Shen, Huanpei; Zhang, Jingjing; Xia, Yiqun; Zou, Peng

doi:10.1016/j.freeradbiomed.2019.06.005

Cited by 36 publications

(18 citation statements)

References 46 publications

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“…Gold complexes are the most effective inhibitors of TrxR, particularly auranofin, which was proved to interact with active site SEC498 . Curcumin, a TrxR inhibitor, was found to irreversibly bind with the active sites SEC498/CYS497, and recently a new analogue of curcumin (WZ26) was shown to be an effective TrxR inhibitor and its binding sites with TrxR (SEC498, CYS497, GLY496, GLN494, LEU493, SER404 LYS123, GLU122, ALA119) were analyzed . After exposing the binding pocket of TrxR in a docking procedure, we found that the key residues around 4 b including SEC498, CYS497, GLY496, GLN494, LEU493, and ASP491.…”

Section: Resultsmentioning

confidence: 99%

“…The Schrödinger Maestro Software was used to predict and analyze the molecular docking of the component 4 b with target protein TrxR (PDB: 3EAN) . The docking procedure was carried out by adding hydrogen atoms, deleting water molecules, and setting the bond orders for crystal proteins and the radius of binding sites.…”

Section: Methodsmentioning

confidence: 99%

“…The template Glide fitness score was set to evaluate the affinity. The possible binding sites of 4 b were analyzed and validated according to the literature …”

Section: Methodsmentioning

confidence: 99%

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A Gold(I) Complex Containing an Oleanolic Acid Derivative as a Potential Anti‐Ovarian‐Cancer Agent by Inhibiting TrxR and Activating ROS‐Mediated ERS

Bian

Sun

Liu

et al. 2020

Chemistry A European J

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Many cancer cells critically rely on antioxidant systems for cell survival and are vulnerable to furthero xidative impairment triggered by agentsg enerating reactive oxygen species (ROS). Therefore, the classical design and development of inhibitors that target antioxidant defense enzymes such as thioredoxin reductase (TrxR) can be ap romising anticancer strategy.H erein, it is shown that ag old(I) complex containing an oleanolic acid derivative (4b)i nduces apopto-sis of ovarian cancerA 2780 cells by activatinge ndoplasmic reticulum stress (ERS). It can inhibitT rxR enzymea ctivity to elevateR OS, mediate ERS and mitochondriald ysfunction, and finally leads to cell cycle arrest and apoptosis of A2780 cells. Notably,t his complex inhibits A2780 xenograft tumor growth accompanied by increased ERS level and decreased TrxR activity in tumor tissues.[a] Dr.[ + + ] These authors contributed equally to this work.[**] ERS:e ndoplasmic reticulums tress, ROS:r eactive oxygen species, TrxR:t hioredoxin reductase.Supporting information and the ORCID identification number(s) for the author(s) of this articlecan be found under: https://doi.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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A Gold(I) Complex Containing an Oleanolic Acid Derivative as a Potential Anti‐Ovarian‐Cancer Agent by Inhibiting TrxR and Activating ROS‐Mediated ERS

Bian

Sun

Liu

et al. 2020

Chemistry A European J

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“…Several studies showed that some ROS inducers can sensitize the tumor cells to cisplatin ( Yang et al, 2017 ; Sun et al, 2018 ; Hsu et al, 2019 ; Zhang et al, 2019 ). Therefore, we set out to determine the synergistic effects of ESI and cisplatin.…”

Section: Resultsmentioning

confidence: 99%

Isodeoxyelephantopin Inactivates Thioredoxin Reductase 1 and Activates ROS-Mediated JNK Signaling Pathway to Exacerbate Cisplatin Effectiveness in Human Colon Cancer Cells

Lin

Chen

et al. 2020

Front. Cell Dev. Biol.

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Colon cancer is one of the leading causes of cancer-related death in the world. The development of new drugs and therapeutic strategies for patients with colon cancer are urgently needed. Isodeoxyelephantopin (ESI), a sesquiterpene lactone isolated from the medicinal plant Elephantopus scaber L., has been reported to exert antitumor effects on several cancer cells. However, the molecular mechanisms underlying the action of ESI is still elusive. In the present study, we found that ESI potently suppressed cell proliferation in human colon cancer cells. Furthermore, our results showed that ESI treatment markedly increased cellular reactive oxygen species (ROS) levels by inhibiting thioredoxin reductase 1 (TrxR1) activity, which leads to activation of the JNK signaling pathway and eventually cell death in HCT116 and RKO cells. Importantly, we found that ESI markedly enhanced cisplatin-induced cytotoxicity in HCT116 and RKO cells. Combination of ESI and cisplatin significantly increased the production of ROS, resulting in activation of the JNK signaling pathway in HCT116 and RKO cells. In vivo, we found that ESI combined with cisplatin significantly suppressed tumor growth in HCT116 xenograft models. Together, our study provide a preclinical proof-of-concept for ESI as a potential strategy for colon cancer treatment.

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“…Natural products from medicinal and nonconventional plants and functional food intake have also been reported by data, which prevent the onset of several diseases or are used as a treatment for several diseases, providing ethnopharmacological knowledge on nutrition therapeutic formulations containing antioxidants on their phytochemical profile [6]. Several studies show their effectiveness in modulating ROS, inflammation, and chemotherapeutic resistance [7,8].…”

Section: Introductionmentioning

confidence: 99%

Hydroethanolic Extract of Solanum paniculatum L. Fruits Modulates ROS and Cytokine in Human Cell Lines

Ferraz

Sussulini

Garcia

et al. 2020

Oxidative Medicine and Cellular Longevity

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Solanum paniculatum L. or popularly known as “jurubeba” is an herbal medicinal plant. A few studies have investigated its biological effects; however, research aimed at elucidating the redox balance effects from its fruits has not been reported so far. ROS interplays in various fields of medicine such as chemotherapy. Here, we evaluated antioxidant and inflammatory activities of the hydroethanolic extract of Solanum Paniculatum L. (HESPL) fruits in breast cancer cells, as well as its phytochemical profile. The antioxidant profile (carotenoids and phenolic compounds) was obtained by HPLC-DAD-UV and HPLC-APCI-MS. Cancer cell lines and human vein endothelial cells (HUVECs) were cultivated and treated with 1.87-30 μg/mL of HESPL for 24 hrs. Cytotoxicity, oxidative, and inflammation biomarkers were evaluated. The dose of 30 μg/mL of the HESPL extract presented cytotoxicity in the MCF-7 cell line. However, for MDA-MB-231, the cytotoxicity was observed in the dose of 1.87 g/mL. The 1.87 μg/mL and 3.75 μg/mL doses decreased the concentration of IL-6 in MCF-7 cells. In the MDA-MB-231 cells, the HESPL did not decrease the IL-6 concentration; however, in the doses of 15 and 30 μg/mL, an increase in this parameter was observed. The HESPL increased IL-1β concentration in HUVECs. The ROS level in MCF-7 was elevated only at the 30 μg/ml dose. Regarding MDA-MB-231, HESPL promoted increased ROS levels at all doses tested. HUVEC showed no increase in ROS under any dose. HESPL treatment may modulate cytotoxicity, ROS, and cytokine levels due to its phytochemical profile, and it has shown an antioxidant or anti-inflammatory effect.

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Curcuminoid WZ26, a TrxR1 inhibitor, effectively inhibits colon cancer cell growth and enhances cisplatin-induced cell death through the induction of ROS

Cited by 36 publications

References 46 publications

A Gold(I) Complex Containing an Oleanolic Acid Derivative as a Potential Anti‐Ovarian‐Cancer Agent by Inhibiting TrxR and Activating ROS‐Mediated ERS

A Gold(I) Complex Containing an Oleanolic Acid Derivative as a Potential Anti‐Ovarian‐Cancer Agent by Inhibiting TrxR and Activating ROS‐Mediated ERS

Isodeoxyelephantopin Inactivates Thioredoxin Reductase 1 and Activates ROS-Mediated JNK Signaling Pathway to Exacerbate Cisplatin Effectiveness in Human Colon Cancer Cells

Hydroethanolic Extract of Solanum paniculatum L. Fruits Modulates ROS and Cytokine in Human Cell Lines

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