The <scp>N</scp>rf2‐<scp>ARE</scp> pathway is associated with <scp>S</scp>chisandrin b attenuating benzo(a)pyrene‐Induced <scp>HTR</scp> cells damages <i>in vitro</i>

Dong, Qulong; Hou, Hanxue; Wu, Jun; Chen, Yaqiong

doi:10.1002/tox.22149

Cited by 18 publications

(11 citation statements)

References 42 publications

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“…Nrf2 has been identified as a key regulator of the inducible expression of antioxidative enzymes, anti-inflammatory proteins and conjugation/detoxification proteins, such as NQO1 and HO-1 [21]. Upon oxidative stress caused by B[a]P or pharmacologic induction, the Nrf2 pathway could be rapidly activated to counteract intracellular ROS generation, thereby attenuating DNA damage and inflammation caused by B[a]P stimulation [21, 22]. The general cytoprotective effect of Nrf2 pathway activation has made it an attractive target for the chemoprevention of B[a]P-induced lung carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…The nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway has been targeted for the prevention of chemical carcinogenesis.Nrf2 has been identified as a key regulator of the inducible expression of antioxidative enzymes, anti-inflammatory proteins and conjugation/detoxification proteins, including NAD(P)H: quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) [21]. Upon oxidative stress caused by B[a]P or pharmacologic induction, the Nrf2 pathway can be rapidly activated to counteract intracellular ROS generation, thereby attenuating DNA damage and inflammation promoted by B[a]P stimulation and contributing to reduced risk of mutation and subsequent lung tumorigenesis [21, 22]. Natural products are well known to exert their protective effects by removing free radicals, modulating the antioxidant defense system and performing carcinogen detoxification.…”

Section: Introductionmentioning

confidence: 99%

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Houttuynia cordata Thunb. and its bioactive compound 2-undecanone significantly suppress benzo(a)pyrene-induced lung tumorigenesis by activating the Nrf2-HO-1/NQO-1 signaling pathway

Lou

Guo

Zhu

et al. 2019

J Exp Clin Cancer Res

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Background Lung cancer remains the most common cause of cancer-related deaths, with a high incidence and mortality in both sexes worldwide. Chemoprevention has been the most effective strategy for lung cancer prevention. Thus, exploring novel and effective candidate agents with low toxicity for chemoprevention is essential and urgent. Houttuynia cordata Thunb. (Saururaceae) ( H. cordata ), which is a widely used herbal medicine and is also popularly consumed as a healthy vegetable, exhibits anti-inflammatory, antioxidant and antitumor activity. However, the chemopreventive effect of H. cordata against benzo(a)pyrene (B[a]P)-initiated lung tumorigenesis and the underlying mechanism remain unclear. Methods A B[a]P-stimulated lung adenocarcinoma animal model in A/J mice in vivo and a normal lung cell model (BEAS.2B) in vitro were established to investigate the chemopreventive effects of H. cordata and its bioactive compound 2-undecanone against lung tumorigenesis and to clarify the underlying mechanisms. Results H. cordata and 2-undecanone significantly suppressed B[a]P-induced lung tumorigenesis without causing obvious systemic toxicity in mice in vivo . Moreover, H. cordata and 2-undecanone effectively decreased B[a]P-induced intracellular reactive oxygen species (ROS) overproduction and further notably protected BEAS.2B cells from B[a]P-induced DNA damage and inflammation by significantly inhibiting phosphorylated H2A.X overexpression and interleukin-1β secretion. In addition, H. cordata and 2-undecanone markedly activated the Nrf2 pathway to induce the expression of the antioxidative enzymes heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO-1). Nrf2 silencing by transfection with Nrf2 siRNA markedly decreased the expression of HO-1 and NQO-1 to diminish the reductions in B[a]P-induced ROS overproduction, DNA damage and inflammation mediated by H. cordata and 2-undecanone. Conclusions H. cordata and 2-undecanone could effectively activate the Nrf2-HO-1/NQO-1 signaling pathway to counteract intracellular ROS generation, thereby attenuating DNA damage and inflammation induced by B[a]P stimulation and playing a role in the chemoprevention of B[a]P-induced lung tumorigenesis. These findings provide new insight into the pharmacological action of H. cordata and indicate that H. cordata is a novel candidate agent for the chemoprevention of lung cancer. Electronic supplementary material The online version of this article (10.1186/s13046-019-1255-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Houttuynia cordata Thunb. and its bioactive compound 2-undecanone significantly suppress benzo(a)pyrene-induced lung tumorigenesis by activating the Nrf2-HO-1/NQO-1 signaling pathway

Lou

Guo

Zhu

et al. 2019

J Exp Clin Cancer Res

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“…The development of a suitable treatment strategy to alleviate the side-effects of DDP should greatly increase its clinical applicability. SchB is a naturally existing small molecule that has been shown to have a variety of cytoprotective activities ( 31 ). To the best of our knowledge, the present study is the first to provide evidence that SchB is able to alleviate DDP-induced renal injury by activating the ERK/NF-κB signaling pathway in vitro .…”

Section: Discussionmentioning

confidence: 99%

Schizandrin B inhibits the cis‑DDP‑induced apoptosis of HK‑2 cells by activating ERK/NF‑κB signaling to regulate the expression of survivin

Liu

Song

et al. 2018

Int J Mol Med

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The nephrotoxicity of cisplatin limits its clinical application. Schizandrin B (SchB) has been demonstrated to have a variety of potential cytoprotective activities. The present study explored the molecular mechanisms by which SchB inhibits the dichlorodiammine platinum (DDP)-induced apoptosis of HK-2 proximal tubule epithelial cells. In vitro assays demonstrated that SchB increased the viability of HK-2 cells, alleviated the cis-DDP-induced activation of caspase-3, reduced apoptosis and improved the nuclear morphology of HK-2 cells. Additionally, the mechanism underlying the cis-DDP-induced apoptosis was indicated to involve the activation of p53, c-Jun-N-terminal kinase (JNK) and p38 signaling. Furthermore, SchB was demonstrated to activate extracellular signal-regulated kinase (ERK) and nuclear factor κB (NF-κB) signaling, and induce the expression of survivin. The inhibition of ERK and NF-κB signaling using U0126 and pyrollidine dithiocarbamate, respectively, inhibited the expression of survivin, whereas blocking the expression of survivin using small interfering RNA inhibited the alleviating effect of SchB on cis-DDP-induced apoptosis as indicated by a reduction in cleaved caspase-3 expression. In conclusion, SchB regulates ERK/NF-κB signaling to induce the expression of survivin, thereby alleviating cis-DDP-induced renal injury.

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“…As one of the major active ingredients in Schisandra chinensis, Sch B has been extensively studied for its diverse pharmacological effects (18). Previous studies have demonstrated that Sch B has potent antioxidant and cytoprotective effects against different types of oxidative stress-induced cell injury in hepatocytes (19)(20)(21), cardiomyocytes (22,23), neurcyte (24,25), kidney tubule cells (26) and trophoblasts (27). In most of these cell types, the antioxidant effects of Sch B derive from Nrf2 activation and subsequent upregulation of antioxidant enzyme expression.…”

Section: Introductionmentioning

confidence: 99%

Schisandrin B protects human keratinocyte-derived HaCaT�cells from tert-butyl hydroperoxide-induced oxidative damage through activating the Nrf2 signaling pathway

et al. 2018

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Schisandrin B (Sch B), an active extract of Schisandra chinensis, has demonstrated antioxidant activity in a number of in vitro and in vivo models. In the present study, the capacity of Sch B to protect against oxidative injury in keratinocytes using the human keratinocyte-derived HacaT cell line was investigated. To induce oxidative injury, tert-Butyl hydroperoxide (tBHP) was employed. The results indicate that Sch B efficiently reduced tBHP-induced cell death, reactive oxygen species (ROS) generation, protein oxidation, lipid peroxidation and dNA damage. Sch B also effectively attenuated the loss of mitochondrial membrane potential (MMP), and restored adenosine triphosphate (ATP) levels in tBHP-injured HacaT cells. Furthermore, Sch B enhanced the expression of key antioxidant enzymes, including catalase, heme oxygenase-1, glutathione peroxidase, and superoxide dismutase, and further engaged the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway by modulating its phosphorylation through activating multiple upstream kinases, including protein kinase B, adenosine monophosphate-activated protein kinase and mitogen-activated protein kinases (MAPKs). The present study suggests that Sch B provides a protective effect in keratinocytes in response to oxidative injury via reinforcing the endogenous antioxidant defense system. Therefore, it may be applied as an adjuvant therapy or in health foods to delay the skin aging process and the onset of skin diseases caused by oxidative stress.

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The Nrf2‐ARE pathway is associated with Schisandrin b attenuating benzo(a)pyrene‐Induced HTR cells damages in vitro

Cited by 18 publications

References 42 publications

Houttuynia cordata Thunb. and its bioactive compound 2-undecanone significantly suppress benzo(a)pyrene-induced lung tumorigenesis by activating the Nrf2-HO-1/NQO-1 signaling pathway

Houttuynia cordata Thunb. and its bioactive compound 2-undecanone significantly suppress benzo(a)pyrene-induced lung tumorigenesis by activating the Nrf2-HO-1/NQO-1 signaling pathway

Schizandrin B inhibits the cis‑DDP‑induced apoptosis of HK‑2 cells by activating ERK/NF‑κB signaling to regulate the expression of survivin

Schisandrin B protects human keratinocyte-derived HaCaT�cells from tert-butyl hydroperoxide-induced oxidative damage through activating the Nrf2 signaling pathway

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