Dithiaarsanes Induce Oxidative Stress-Mediated Apoptosis in HL-60 Cells by Selectively Targeting Thioredoxin Reductase

Liu, Yaping; Duan, Dongzhu; Yao, Juan; Zhang, Baoxin; Peng, Shoujiao; Ma, Haiying; Song, Yanlin; Fang, Jianguo

doi:10.1021/jm500221p

Cited by 109 publications

(135 citation statements)

References 68 publications

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“…Several studies have showed that curcumin induced apoptosis in human lung cancer cells through generation of reactive oxygen species (ROS) . Enhancement of ROS production is also frequently observed during induction of apoptosis by anticancer agents . Therefore, generation of ROS by curcumin to trigger cancer cell death may be an attractive strategy for lung cancer.…”

Section: Introductionmentioning

confidence: 99%

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Curcumin analog L48H37 induces apoptosis through ROS‐mediated endoplasmic reticulum stress and STAT3 pathways in human lung cancer cells

Chen

Xia

Zou

et al. 2017

Molecular Carcinogenesis

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Lung cancer is the leading cause of cancer-related deaths. Curcumin is a well-known natural product with anticancer ability, however, its poor bioavailability and pharmacokinetic profiles have limited its application in anticancer therapy. Previously, we reported that L48H37, a novel analog of curcumin with higher bioavailability, ameliorated LPS-induced inflammation, but the anticancer effect of L48H37 is still unknown. In the present study, we have investigated the effects of L48H37 in human lung cancer cells. Our results show that L48H37 decreases lung cancer cell growth and colony formation. These alterations were mediated through induction of G2/M cell cycle arrest and apoptosis in lung cancer cells. After L48H37 treatment, ER stress-related proteins were increased, and the expression of p-STAT3 was decreased in a dose-dependent manner. L48H37 also induced the accumulation of ROS in lung cancer cells, and pretreatment with NAC could fully reverse L48H37-induced reactive oxygen species (ROS) increase. Blocking ROS was able to reverse L48H37-induced endoplasmic reticulum (ER) stress, cell cycle arrest, and apoptosis. Finally, we show that L48H37 inhibits the growth of lung cancer xenografts without exhibiting toxicity. Treatment of mice bearing human lung cancer xenografts with L48H37 was also associated with indices of ER stress activation. In summary, our results provide evidence for a novel anti-tumor candidate for the treatment of lung cancer.

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Section: Introductionmentioning

confidence: 99%

“…12,13 Enhancement of ROS production is also frequently observed during induction of apoptosis by anticancer agents. [14][15][16] Therefore, generation of ROS by curcumin to trigger cancer cell death may be an attractive strategy for lung cancer. However, clinical application of curcumin is limited by its poor bioavailability and pharmacokinetic profile.…”

mentioning

confidence: 99%

Curcumin analog L48H37 induces apoptosis through ROS‐mediated endoplasmic reticulum stress and STAT3 pathways in human lung cancer cells

Chen

Xia

Zou

et al. 2017

Molecular Carcinogenesis

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“…Similar with ATO associated with mitochondrial dysfunction, more and more reports have shown that organic arsenicals can induce the mitochondria‐mediated or ROS‐mediated cell death . F16 as the cationic form of PVI could accumulate into mitochondria and cause mitochondria dysfunction.…”

Section: Resultsmentioning

confidence: 89%

Dual Inhibition of Pyruvate Dehydrogenase Complex and Respiratory Chain Complex Induces Apoptosis by a Mitochondria‐Targeted Fluorescent Organic Arsenical in vitro and in vivo

et al. 2020

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Based on the potential therapeutic value in targeting mitochondria and the fluorophore tracing ability, a fluorescent mitochondria‐targeted organic arsenical PDT‐PAO‐F16 was fabricated, which not only visualized the cellular distribution, but also exerted anti‐cancer activity in vitro and in vivo via targeting pyruvate dehydrogenase complex (PDHC) and respiratory chain complexes in mitochondria. In details, PDT‐PAO‐F16 mainly accumulated into mitochondria within hours and suppressed the activity of PDHC resulting in the inhibition of ATP synthesis and thermogenesis disorder. Moreover, the suppression of respiratory chain complex I and IV accelerated the mitochondrial dysfunction leading to caspase family‐dependent apoptosis. In vivo, the acute promyelocytic leukemia was greatly alleviated in the PDT‐PAO‐F16 treated group in APL mice model. Our results demonstrated the organic arsenical precursor with fluorescence imaging and target‐anticancer efficacy is a promising anticancer drug.

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“…Firstly, we employed the fluorescent probe TRFS-green to determine the TrxR activity as this is a very convenient assay by simply treating the cells with the probe and watch the fluorescence change after a few hours 35,39 . Since 6-S dose-dependently elevated a panel of phase II genes, we then analyzed the corresponding gene products by determining their activity and contents.…”

Section: Upregulation Of Antioxidant Defense System In Pc12 Cellsmentioning

confidence: 99%

Activation of Nrf2 target enzymes conferring protection against oxidative stress in PC12 cells by ginger principal constituent 6-shogaol

et al. 2015

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Natural compounds containing phenoxyl groups and/or Michael acceptor units appear to possess antioxidant and cytoprotective properties. The ginger principal constituent 6-shogaol (6-S) represents one of such compounds. In this study, we reported that 6-S efficiently scavenges various free radicals in vitro, and displays remarkable cytoprotection against oxidative stress-induced cell damage in the neuron-like rat pheochromocytoma cell line, PC12 cells. Pretreatment of PC12 cells with 6-S significantly upregulates a series of phase II antioxidant molecules, such as glutathione, heme oxygenase 1, NAD(P)H: quinone oxidoreductase 1, thioredoxin reductase 1, and thioredoxin 1. A mechanistic study revealed that 6-S enhanced the translocation of Nrf2 from the cytosol to the nucleus and knockdown of Nrf2 abolished such protection, indicating that this cytoprotection is mediated by the activation of the transcription factor Nrf2. Another ginger constituent 6-gingerol (6-G), having a similar structure of 6-S but lacking the alpha,beta-unsaturated ketone structure (Michael acceptor moiety), failed to shelter PC12 cells from oxidative stress. Our results demonstrate that 6-S is a novel small molecule activator of Nrf2 in PC12 cells, and suggest that 6-S might be a potential candidate for the prevention of oxidative stress-mediated neurodegenerative disorders.

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Dithiaarsanes Induce Oxidative Stress-Mediated Apoptosis in HL-60 Cells by Selectively Targeting Thioredoxin Reductase

Cited by 109 publications

References 68 publications

Curcumin analog L48H37 induces apoptosis through ROS‐mediated endoplasmic reticulum stress and STAT3 pathways in human lung cancer cells

Curcumin analog L48H37 induces apoptosis through ROS‐mediated endoplasmic reticulum stress and STAT3 pathways in human lung cancer cells

Dual Inhibition of Pyruvate Dehydrogenase Complex and Respiratory Chain Complex Induces Apoptosis by a Mitochondria‐Targeted Fluorescent Organic Arsenical in vitro and in vivo

Activation of Nrf2 target enzymes conferring protection against oxidative stress in PC12 cells by ginger principal constituent 6-shogaol

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