Luteolin protects rat PC 12 and C6 cells against MPP+ induced toxicity via an ERK dependent Keapl-Nrf2-ARE pathway

Wruck, C.; Claussen, Malte Christian; Fuhrmann, Gregor; Romer, Lewis H.; Schulz, Anja; Pufe, Thomas; Waetzig, Vicki; Peipp, Matthias; Herdegen, Thomas; Götz, Mario E.

doi:10.1007/978-3-211-73574-9_9

Cited by 140 publications

(95 citation statements)

References 49 publications

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“…In addition, We also demonstrated that luteolin was a potential Nrf2 inhibitor and enhanced sensitivity of A549 cells to chemotherapeutics by promoting degradation of Nrf2 mRNA (Tang et al, 2011). Notably, luteolin had different effects on the Nrf2 signaling pathway in different cell types if activated Nrf2 expression in PC12 and C6 neural cells and protected them from oxidative stress mediated by ERK (Wruck et al, 2007;Lin et al, 2010). Luteolin can induce HO-1 expression in myocardial H9c2 cells and protect them by activating Akt and ERK to activate the Nrf2 signaling pathway (Sun et al, 2012).…”

Section: Discussionmentioning

confidence: 78%

Luteolin Sensitizes Two Oxaliplatin-Resistant Colorectal Cancer Cell Lines to Chemotherapeutic Drugs Via Inhibition of the Nrf2 Pathway

Chian

Li²,

Wang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Oxaliplatin is a first-line therapy for colorectal cancer, but cancer cell resistance to the drug compromises its efficacy. To explore mechanisms of drug resistance, we treated colorectal cancer cells (HCT116 and SW620) long-term with oxaliplatin and established stable oxaliplatin-resistant lines (HCT116-OX and SW620-OX). Compared with parental cell lines, IC 50 s for various chemotherapeutic agents (oxaliplatin, cisplatin and doxorubicin) were increased in oxaliplatin-resistant cell lines and this was accompanied by activation of nuclear factor erythroid-2 p45-related factor 2 (Nrf2) and NADPH quinone oxidoreductase 1 (NQO1) . Furthermore, luteolin inhibited the Nrf2 pathway in oxaliplatin-resistant cell lines in a dose-dependent manner. Luteolin also inhibited Nrf2 target gene [NQO1, heme oxygenase-1 (HO-1) and GSTα1/2] expression and decreased reduced glutathione in wild type mouse small intestinal cells. There was no apparent effect in Nrf2-/-mice. Luteolin combined with other chemotherapeutics had greater anti-cancer activity in resistant cell lines (combined index values below 1), indicating a synergistic effect. Therefore, adaptive activation of Nrf2 may contribute to the development of acquired drug-resistance and luteolin could restore sensitivity of oxaliplatin-resistant cell lines to chemotherapeutic drugs. Inhibition of the Nrf2 pathway may be the mechanism for this restored therapeutic response.

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Section: Discussionmentioning

confidence: 78%

Luteolin Sensitizes Two Oxaliplatin-Resistant Colorectal Cancer Cell Lines to Chemotherapeutic Drugs Via Inhibition of the Nrf2 Pathway

Chian

Li²,

Wang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…The beststudied members of this family, ERK1/2, have been considered critical in promoting cell survival against oxidative stress in cultured primary neurons (Hota, Hota et al 2012;Sanchez et al 2012) as well as PC12 cells (Wruck et al 2007;Xiao et al 2011). However, these studies utilized the pharmacological inhibitors U0126 and PD98059, which have been previously used as selective inhibitors of the ERK1/2 signaling pathway but recently reported to effectively inhibit ERK5 signaling pathway as well (Suzaki et al 2004;Su et al 2011).…”

Section: Discussionmentioning

confidence: 99%

ERK5/KLF4 signaling as a common mediator of the neuroprotective effects of both nerve growth factor and hydrogen peroxide preconditioning

Sun

Cunningham

et al. 2014

AGE

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Oxidative stress has long been implicated in the pathogenesis of various neurodegenerative disorders such as Alzheimer's disease and stroke. While high levels of oxidative stress are generally associated with cell death, a slight rise of reactive oxygen species (ROS) levels can be protective by "preconditioning" cells to develop a resistance against subsequent challenges. However, the mechanisms underlying such preconditioning (PC)-induced protection are still poorly understood. Previous studies have supported a role of ERK5 (mitogen-activated protein [MAP] kinase 5) in neuroprotection and ischemic tolerance in the hippocampus. In agreement with these findings, our data suggest that ERK5 mediates both hydrogen peroxide (H 2 O 2 )-induced PC as well as nerve growth factor (NGF)-induced neuroprotection. Activation of ERK5 partially rescued pheochromocytoma PC12 cells as well as primary hippocampal neurons from H 2 O 2 -caused death, while inhibition of ERK5 abolished NGF or PC-induced protection. These results implicate ERK5 signaling as a common downstream pathway for NGF and PC.Furthermore, both NGF and PC increased the expression of the transcription factor, KLF4, which can initiate an anti-apoptotic response in various cell types. Induction of KLF4 by NGF or PC was blocked by siERK5, suggesting that ERK5 is required in this process. siKLF4 can also attenuate NGF-or PC-induced neuroprotection. Overexpression of active MEK5 or KLF4 in H 2 O 2 -stressed cells increased Bcl-2/Bax ratio and the expression of NAIP (neuronal apoptosis inhibitory protein). Taken together, our data suggest that ERK5/KLF4 cascade is a common signaling pathway shared by at least two important mechanisms by which neurons can be protected from cell death.

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“…Luteolin, one of the common natural flavonoids, possesses high antioxidant capability (Galati et al, 2001). It has been reported that luteolin increased the survival of PC12 cells treated with hydrogen peroxide (Dajas et al, 2003), protected PC12 cells against apoptosis induced by N-methyl-4-phenylpyridinium (Wruck et al, 2007) as well as suppressed the lipopolysaccharide-elicited inflammatory events in mouse alveolar macrophages by inhibiting the generation of ROS (Chen et al, 2007). However, at concentration up to 100 µM, luteolin reduced cell viability in PC12 cells (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of luteolin against apoptosis induced by 6-hydroxydopamine on rat pheochromocytoma PC12 cells

Guo¹,

Fan²,

Yu³

et al. 2012

Pharmaceutical Biology

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Luteolin protects rat PC 12 and C6 cells against MPP+ induced toxicity via an ERK dependent Keapl-Nrf2-ARE pathway

Cited by 140 publications

References 49 publications

Luteolin Sensitizes Two Oxaliplatin-Resistant Colorectal Cancer Cell Lines to Chemotherapeutic Drugs Via Inhibition of the Nrf2 Pathway

Luteolin Sensitizes Two Oxaliplatin-Resistant Colorectal Cancer Cell Lines to Chemotherapeutic Drugs Via Inhibition of the Nrf2 Pathway

ERK5/KLF4 signaling as a common mediator of the neuroprotective effects of both nerve growth factor and hydrogen peroxide preconditioning

Neuroprotective effects of luteolin against apoptosis induced by 6-hydroxydopamine on rat pheochromocytoma PC12 cells

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