Ferulate, an Active Component of Wheat Germ, Ameliorates Oxidative Stress-Induced PTK/PTP Imbalance and PP2A Inactivation

Koh, Eunmi; Lee, Eun Kyeong; Song, Chi Hun; Song, Jung Sang; Chung, Hae Young; Chae, Chang Hoon; Jung, Kyung Jin

doi:10.5487/tr.2018.34.4.333

Cited by 10 publications

(7 citation statements)

References 37 publications

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“…www.nature.com/scientificreports www.nature.com/scientificreports/ such as dual specificity phosphatase 1 (DUSP1) 54 or protein phosphatase 2 A (PP2A) 55,56 , can possibly contribute to it.…”

Section: Discussionmentioning

confidence: 99%

trans-Fatty acids facilitate DNA damage-induced apoptosis through the mitochondrial JNK-Sab-ROS positive feedback loop

Hirata

Inoue

Suzuki

et al. 2020

Sci Rep

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trans-fatty acids (tfAs) are unsaturated fatty acids that contain one or more carbon-carbon double bonds in trans configuration. Epidemiological evidence has linked TFA consumption with various disorders, including cardiovascular diseases. However, the underlying pathological mechanisms are largely unknown. Here, we show a novel toxic mechanism of TFAs triggered by DNA damage. We found that elaidic acid (EA) and linoelaidic acid, major TFAs produced during industrial food manufacturing (so-called as industrial TFAs), but not their corresponding cis isomers, facilitated apoptosis induced by doxorubicin. Consistently, EA enhanced UV-induced embryonic lethality in C. elegans worms. The pro-apoptotic action of EA was blocked by knocking down Sab, a c-Jun N-terminal kinase (JNK)interacting protein localizing at mitochondrial outer membrane, which mediates mutual amplification of mitochondrial reactive oxygen species (ROS) generation and JNK activation. EA enhanced doxorubicin-induced mitochondrial ROS generation and JNK activation, both of which were suppressed by Sab knockdown and pharmacological inhibition of either mitochondrial ROS generation, JNK, or Src-homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1) as a Sab-associated protein. These results demonstrate that in response to DNA damage, TFAs drive the mitochondrial JNK-Sab-ROS positive feedback loop and ultimately apoptosis, which may provide insight into the common pathogenetic mechanisms of diverse TFA-related disorders. trans-Fatty acids (TFAs) are defined as unsaturated fatty acids containing one or more carbon-carbon double bonds in trans configuration. TFAs, such as elaidic acid (EA, C18:1 t9) and linoelaidic acid (LEA, C18:2 t9,t12), so-called as industrial TFAs, are produced during the food manufacturing processes, mainly through partial hydrogenation of vegetable and fish oils that contain cis isomers of TFAs, hereafter referred to as cis-fatty acids (CFAs) 1. On the other hand, TFAs such as trans-vaccenic acid (TVA, C18:1 t11), so-called as ruminant TFAs, are produced via enzymatic isomerization of CFAs by ruminal microbes in cows and sheep, and are present in dairy products and meat 1. Compelling epidemiological evidence has shown that the intake of TFAs, particularly industrial TFAs, increases the risk of various disorders, such as systemic inflammation, metabolic syndrome, neurodegenerative disorders, and cardiovascular diseases (CVDs) 2-5. However, few studies have focused on the mechanisms of action of TFAs, and the molecular mechanisms underlying TFA-related disorders remain to be elucidated. Among TFA-related disorders, TFAs have been most highly linked with atherosclerosis, one of the major cause of CVDs, and the underlying mechanisms have been explained by their deleterious effects on vascular endothelial functions and lipoprotein regulation 3,6-10. Importantly, we have recently revealed a novel toxic function of TFAs as an enhancer of inflammatory signaling and cell death induced by extracellular ATP, one of the damage-assoc...

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Section: Discussionmentioning

confidence: 99%

trans-Fatty acids facilitate DNA damage-induced apoptosis through the mitochondrial JNK-Sab-ROS positive feedback loop

Hirata

Inoue

Suzuki

et al. 2020

Sci Rep

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“…The production of ROS was measured using DCF-DA, as described previously [72]. At the end of the treatment with isorhamnetin for defined periods in the presence or absence of NAC (Sigma-Aldrich Chemical Co.), cells were washed with PBS and incubated with 10 μM DCF-DA (Invitrogen, Carlsbad, CA, USA) in the dark at 37 °C for 20 min.…”

Section: Methodsmentioning

confidence: 99%

Isorhamnetin Induces Cell Cycle Arrest and Apoptosis Via Reactive Oxygen Species-Mediated AMP-Activated Protein Kinase Signaling Pathway Activation in Human Bladder Cancer Cells

Park

Cha

Choi

et al. 2019

Cancers

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Isorhamnetin is an O-methylated flavonol that is predominantly found in the fruits and leaves of various plants, which have been used for traditional herbal remedies. Although several previous studies have reported that this flavonol has diverse health-promoting effects, evidence is still lacking for the underlying molecular mechanism of its anti-cancer efficacy. In this study, we examined the anti-proliferative effect of isorhamnetin on human bladder cancer cells and found that isorhamnetin triggered the gap 2/ mitosis (G2/M) phase cell arrest and apoptosis. Our data showed that isorhamnetin decreased the expression of Wee1 and cyclin B1, but increased the expression of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP1, and increased p21 was bound to Cdk1. In addition, isorhamnetin-induced apoptosis was associated with the increased expression of the Fas/Fas ligand, reduced ratio of B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein (Bax) expression, cytosolic release of cytochrome c, and activation of caspases. Moreover, isorhamnetin inactivated the adenosine 5′-monophosphate-activated protein kinase (AMPK) signaling pathway by diminishing the adenosine triphosphate (ATP) production due to impaired mitochondrial function. Furthermore, isorhamnetin stimulated production of intracellular reactive oxygen species (ROS); however, the interruption of ROS generation using a ROS scavenger led to an escape from isorhamnetin-mediated G2/M arrest and apoptosis. Collectively, this is the first report to show that isorhamnetin inhibited the proliferation of human bladder cancer cells by ROS-dependent arrest of the cell cycle at the G2/M phase and induction of apoptosis. Therefore, our results provide an important basis for the interpretation of the anti-cancer mechanism of isorhamnetin in bladder cancer cells and support the rationale for the need to evaluate more precise molecular mechanisms and in vivo anti-cancer properties.

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“…The production of ROS was measured using DCF-DA, as described previously (Koh et al 2018). At the end of the treatment with isorhamnetin for defined periods in the presence or absence of NAC, a well-known antioxidant, cells were incubated with 10 μM DCF-DA in the dark at 37°C for 20 min.…”

Section: Measurement Of Ros Production and Mitochondrial Membrane Potmentioning

confidence: 99%

Isorhamnetin induces ROS-dependent cycle arrest at G2/M phase and apoptosis in human hepatocarcinoma Hep3B cells

Choi

2019

gpb

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Isorhamnetin is a 3'-O-methylated metabolite of quercetin that is found predominantly in a variety of medicinal plants. Although many previous studies have reported that this flavonol has diverse health-promoting effects, evidence for the underlying molecular mechanism of anti-cancer efficacy is still lacking. In this study, it was examined the anti-proliferative effect of isorhamnetin on human hepatocarcinoma Hep3B cells, and found that isorhamnetin induced cell cycle arrest at G2/M phase and apoptosis. Isorhamnetin-induced G2/M arrest was associated with decreased expression of proliferating cell nuclear antigen as well as cyclin A and cyclin B1. However, isorhamnetin increased expression of p21WAF1/CIP1, a cyclin-dependent kinase (Cdk) inhibitor, and increased p21 complexed with Cdk2 and Cdc2. In addition, isorhamnetin-induced apoptosis was associated with increased expression of Fas/Fas ligand, reduced ratio of Bcl-2/Bax expression, truncation of Bid, cytosolic release of cytochrome c, and activation of caspase-8,-9 and-3. Isorhamnetin also enhanced intracellular levels of reactive oxygen species (ROS), while the addition of N-acetyl cysteine (NAC), a ROS inhibitor, significantly diminished isorhamnetin-induced mitochondrial dysfunction. Furthermore, the interruption of ROS generation using NAC significantly attenuated isorhamnetinmediated G2/M arrest and apoptosis. Collectively, this is the first report to show that isorhamnetin inhibited the proliferation of human hepatocarcinoma cells by ROS-dependent arrest of the cell cycle at the G2/M phase and induction of apoptosis.

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Ferulate, an Active Component of Wheat Germ, Ameliorates Oxidative Stress-Induced PTK/PTP Imbalance and PP2A Inactivation

Cited by 10 publications

References 37 publications

trans-Fatty acids facilitate DNA damage-induced apoptosis through the mitochondrial JNK-Sab-ROS positive feedback loop

trans-Fatty acids facilitate DNA damage-induced apoptosis through the mitochondrial JNK-Sab-ROS positive feedback loop

Isorhamnetin Induces Cell Cycle Arrest and Apoptosis Via Reactive Oxygen Species-Mediated AMP-Activated Protein Kinase Signaling Pathway Activation in Human Bladder Cancer Cells

Isorhamnetin induces ROS-dependent cycle arrest at G2/M phase and apoptosis in human hepatocarcinoma Hep3B cells

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