EGR-1/Bax pathway plays a role in vitamin E δ-tocotrienol-induced apoptosis in pancreatic cancer cells

Wang, Chen; Husain, Kazim; Zhang, Anying; Centeno, Barbara A.; Chen, Dung Tsa; Tong, Zhongsheng; Sebti, Saı̈d M.; Malafa, Mokenge P.

doi:10.1016/j.jnutbio.2015.02.008

Cited by 44 publications

(39 citation statements)

References 75 publications

(87 reference statements)

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“…The molecular mechanisms reported for the antiproliferation, proapoptosis, and other anticancer activities of δ-T3 and γ-T3, as depicted in Figure 3, involve the inhibitory effects on WNT signaling, [116][117][118][119][120] NF-κB pathway, [121][122][123] NOTCH signaling, [123][124][125][126] and AKT/mTOR signaling 127,128 ; and/or the activation of STAT3, 129,130 SRC kinase, 130 AMPK, 131 and receptor tyrosine kinases HER3/HER4. 132,133 The inhibition of proliferation and induction apoptosis were also reported to be mediated through tocotrienol-induced activation of EGR-1/BAX pathway, 134 upregulation of miR-34a, 125 miR-429, 135 p27/ CDKN1B, 136 and PPAR-γ, 137 disruption of lipid raft 132,133 and modification of mitochondria membrane and activation of proapoptosis genes. [138][139][140] Moreover, tocotrienols and their 13′-COOH metabolites modulate sphingolipid metabolism through inhibition of dihydroceramide desaturase.…”

Section: Studies With Tocotrienolsmentioning

confidence: 99%

Vitamin E and cancer prevention: Studies with different forms of tocopherols and tocotrienols

Yang

Luo

Zeng

et al. 2020

Molecular Carcinogenesis

127

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α‐Tocopherol (α‐T) is the major form of vitamin E (VE) in animals and has the highest activity in carrying out the essential antioxidant functions of VE. Because of the involvement of oxidative stress in carcinogenesis, the cancer prevention activity of α‐T has been studied extensively. Lower VE intake or nutritional status has been shown to be associated with increased cancer risk, and supplementation of α‐T to populations with VE insufficiency has shown beneficial effects in lowering the cancer risk in some intervention studies. However, several large intervention studies with α‐T conducted in North America have not demonstrated a cancer prevention effect. More recent studies have centered on the γ‐ and δ‐forms of tocopherols and tocotrienols (T3). In comparison with α‐T, these forms have much lower systemic bioavailability but have shown stronger cancer‐preventive activities in many studies in animal models and cell lines. γ‐T3 and δ‐T3 generally have even higher activities than γ‐T and δ‐T. In this article, we review recent results from human and laboratory studies on the cancer‐preventive activities of different forms of tocopherols and tocotrienols, at nutritional and pharmacological levels. We aim to elucidate the possible mechanisms of the preventive actions and discuss the possible application of the available information for human cancer prevention by different VE forms.

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Section: Studies With Tocotrienolsmentioning

confidence: 99%

Vitamin E and cancer prevention: Studies with different forms of tocopherols and tocotrienols

Yang

Luo

Zeng

et al. 2020

Molecular Carcinogenesis

127

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“…In the previously discussed studies involving curcumin and resveratrol it is important to note that thought these agents can exhibit antioxidant activity, it is likely that their anti-cancer effects are mediated through other modes of action in addition to their antioxidant properties. Vitamin E, another well-characterized antioxidant, suppresses Panc1, MiaPaca2 and BxPC3 pancreatic cancer cell growth in vitro [118,119]. In addition, mice expressing oncogenic KRas G12D in their pancreas survived longer when they were treated with vitamin E, and their PanIN failed to progress [120].…”

Section: Targeting Ros In Pda Development and Progressionmentioning

confidence: 99%

“…The efficacy of Vitamin C has also been demonstrated in a mouse model of KRas G12D driven colorectal cancer, where it was shown to inhibit tumor growth in vivo [122]. In contrast to studies where application of Vitamin E was shown to produce anti-proliferative effects in PDA cells [118,119], in lung cancer cells with oncogenic KRas G12D mutation, vitamin E application actually enhanced cell growth [123]. The varied outcomes between these studies could be explained by differences in the concentration of Vitamin E used, duration of Vitamin E application, variations in basal ROS levels or genetic variations in key tumor suppressor or oncogenes within cells.…”

Section: Targeting Ros In Pda Development and Progressionmentioning

confidence: 99%

Targeting reactive oxygen species in development and progression of pancreatic cancer

Durand

Störz

2016

Expert Review of Anticancer Therapy

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Introduction Pancreatic ductal adenocarcinoma (PDA) is characterized by expression of oncogenic KRas which drives all aspects of tumorigenesis. Oncogenic KRas induces the formation of reactive oxygen species (ROS) which have been implicated in initiation and progression of PDA. To facilitate tumor promoting levels and to avoid oncogene-induced senescence or cytotoxicity, ROS homeostasis in PDA cells is balanced by additional up-regulation of antioxidant systems. Areas Covered We examine the sources of ROS in PDA, the mechanisms by which ROS homeostasis is maintained, and the biological consequences of ROS in PDA. Additionally, we discuss the potential mechanisms for targeting ROS homoeostasis as a point of therapeutic intervention. An extensive review of the relevant literature as it relates to the topic was conducted using PubMed. Expert Commentary Even though oncogenic mutations in the KRAS gene have been detected in over 95% of human pancreatic adenocarcinoma, targeting its gene product, KRas, has been difficult. The dependency of PDA cells on balancing ROS homeostasis could be an angle for new prevention or treatment strategies. These include use of antioxidants to prevent formation or progression of precancerous lesions, or methods to increase ROS in tumor cells to toxic levels.

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“…By inducing cell cycle arrest and apoptosis. Moreover, it was demonstrated that δ‐tocotrienol (Delta), a natural form of vitamin E, has an anticancer property against pancreatic cancer (Husain et al, ; Wang et al, ). However, there are no data about its antioxidant effect against the OTA nephrotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Effects of δ‐tocotrienol on ochratoxin A—induced nephrotoxicity in rats

Damiano¹,

Navas²,

Lombari

et al. 2018

Journal Cellular Physiology

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Ochratoxin A (OTA), is a natural contaminant of the food chain worldwide involved in the development of different type of cancers in animals and humans. Several studies suggested that oxidative damage might contribute to increase the cytotoxicity and carcinogenicity capabilities of OTA. The aim of this study was to evaluate the possible protective effect of δ-tocotrienol (Delta), a natural form of vitamin E, against OTA-induced nephrotoxicity. Male Sprague-Dawley rats were treated with OTA and/or Delta by gavage for 14 days. Our results shown that OTA treatment induced the increase of reactive oxigen species production correlated to a strong reduction of Glomerular Filtration Rate (GFR) and absoluted fluid reabsorption (Jv) with conseguent significant increase in blood pressure. Consistent, we noted in the kidney of rats treated with OTA, an increase in malondialdheyde and dihydroethidium production and a reduction of the activity of the catalase, superoxide dismutase, and glutathione peroxidase. Conversly, in the rat group subjected to the concomitant treatment OTA plus Delta, we observed the restored effect, compared the OTA treatment group, on blood pressure, GFR, Jv, and all activities of renal antioxidant enzymes. Finally, as far as concern the tissue damage induced by OTA and measured evaluating fibronectin protein levels, we observed that in OTA plus Delta group this effect is not restored. Our findings releval that a mechanism underlying the renal toxicity induced by OTA is the oxidative stress and provide a new rationale to use a Delta in order to protect, at least in part, against OTA-induced nephrotoxicity.

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EGR-1/Bax pathway plays a role in vitamin E δ-tocotrienol-induced apoptosis in pancreatic cancer cells

Cited by 44 publications

References 75 publications

Vitamin E and cancer prevention: Studies with different forms of tocopherols and tocotrienols

Vitamin E and cancer prevention: Studies with different forms of tocopherols and tocotrienols

Targeting reactive oxygen species in development and progression of pancreatic cancer

Effects of δ‐tocotrienol on ochratoxin A—induced nephrotoxicity in rats

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