Cardioprotection with palm tocotrienol: antioxidant activity of tocotrienol is linked with its ability to stabilize proteasomes

Das, Samarjit; Powell, Saul R.; Wang, Ping; Divald, András; Nesaretnam, Kalanithi; Tósaki, Árpád; Cordis, Gerald A.; Maulik, Nilanjana; Das, Dipak K.

doi:10.1152/ajpheart.01285.2004

Cited by 72 publications

(49 citation statements)

References 36 publications

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“…Some evidence has suggested that T3s have greater potential physiologic functions than TPs (7,8). T3 has been shown to mediate its activity against a variety of chronic diseases, including cardiovascular diseases, neurologic diseases, diabetes, and cancer (9)(10)(11)(12)(13)(14). T3s have shown anticancer activity against cancers such as colon, breast, liver, lung, kidney, prostate, skin, and other cancers both in vitro (15)(16)(17)(18)(19)(20) and in vivo (21)(22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

γ-Tocotrienol Promotes TRAIL-Induced Apoptosis through Reactive Oxygen Species/Extracellular Signal-Regulated Kinase/p53–Mediated Upregulation of Death Receptors

Kannappan

Ravindran

Prasad

et al. 2010

Molecular Cancer Therapeutics

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor superfamily, is in clinical trials for cancer therapy, but its anticancer potential is limited by the development of resistance. We investigated the ability of tocotrienol (T3), an unsaturated vitamin E present in palm oil, rice bran, barley, oats, and wheat germ, to sensitize tumor cells to TRAIL. Results from esterase staining, colony formation, caspase activation, and sub-G 1 cell cycle arrest revealed that γ-T3 can sensitize human colon cancer cells to TRAIL. When examined for the mechanism, we found that γ-T3 significantly downregulated the expression of antiapoptotic proteins (c-IAP2 and Bcl-xL). We also found that γ-T3, but not tocopherol, induced the expression of the TRAIL receptors death receptor (DR)-4 and DR5. This induction was not cell type specific, as upregulation was also found in pancreatic, kidney, and leukemic cells. Upregulation of DRs by γ-T3 required the production of reactive oxygen species (ROS), and sequestering of ROS abolished both upregulation of the receptors and potentiation of TRAIL-induced apoptosis. Induction of DRs by γ-T3 also required activation of extracellular signal-regulated kinase 1 (ERK1), as silencing of ERK1 by specific siRNA abrogated the upregulation of TRAIL receptors. Further, induction of DRs by γ-T3 required the expression of p53 and Bax, as no induction of the receptors was found in colon cancer cells with deletion of these genes. Overall, our results show that γ-T3 sensitizes tumor cells to TRAIL by upregulating DRs through the ROS/ ERK/p53 pathway and by downregulating cell survival proteins. Mol Cancer Ther; 9(8); 2196-207. ©2010 AACR.

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Section: Introductionmentioning

confidence: 99%

γ-Tocotrienol Promotes TRAIL-Induced Apoptosis through Reactive Oxygen Species/Extracellular Signal-Regulated Kinase/p53–Mediated Upregulation of Death Receptors

Kannappan

Ravindran

Prasad

et al. 2010

Molecular Cancer Therapeutics

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“…We (21) have shown that the proteasome may become dysfunctional as a result of ischemia. TRF was observed to partially protect the proteasome, which may have facilitated the degradation of phospho-c-Src (7).…”

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confidence: 98%

“…Recently, tocotrienols have been found to be effective in protecting the central nervous system compared with ␣-tocopherol, and tocotrienol inhibited glutamate-induced pp60 c-Src kinase activation in HT4 neuronal cells (27). Tocotrienols have also been found to provide cardioprotection against several cardiovascular diseases (7,(23)(24)(25). A recent study showed that cardioprotection with palm tocotrienols [the tocotrienol-rich fraction (TRF)] was linked with their ability to stabilize proteasomes (7).…”

mentioning

confidence: 99%

“…Tocotrienols have also been found to provide cardioprotection against several cardiovascular diseases (7,(23)(24)(25). A recent study showed that cardioprotection with palm tocotrienols [the tocotrienol-rich fraction (TRF)] was linked with their ability to stabilize proteasomes (7). We (21) have shown that the proteasome may become dysfunctional as a result of ischemia.…”

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confidence: 99%

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Cardioprotection with palm oil tocotrienols: comparision of different isomers

Das¹,

Lekli²,

M³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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A recent study from our laboratory indicated the cardioprotective ability of the tocotrienolrich fraction (TRF) from red palm oil. The present study compared cardioprotective abilities of different isomers of tocotrienol against TRF as recently tocotrienol has been found to function as a potent neuroprotective agent against stroke. Rats were randomly assigned to one of the following groups: animals were given, by gavage, either 0.35%, 1%, or 3.5% TRF for two different periods of time (2 or 4 wk) or 0.03, 0.3, and 3 mg/kg body wt of one of the isomers of tocotrienol (␣, ␥, or ␦) for 4 wk; control animals were given, by gavage, vehicle only. After 2 or 4 wk, rats were killed, and their hearts were then subjected to 30 min of global ischemia followed by 2 h of reperfusion. Dose-response and time-response experiments revealed that the optimal concentration for TRF was 3.5% TRF and 0.3 mg/kg body wt of tocotrienol given for 4 wk. TRF as well as all the isomers of tocotrienol used in our study provided cardioprotection, as evidenced by their ability to improve postischemic ventricular function and reduce myocardial infarct size. The ␥-isoform of tocotrienol was the most cardioprotective of all the isomers followed by the ␣-and ␦-isoforms. The molecular mechanisms of cardioprotection afforded by tocotrienol isoforms were probed by evaluating their respective abilities to stabilize the proteasome, allowing it to maintain a balance between prodeath and prosurvival signals. Our results demonstrated that tocotrienol isoforms reduced c-Src but increased the phosphorylation of Akt, thus generating a survival signal.

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“…One study indicated that tocotrienol-rich fraction was able to reduce myocardial infarct size, improve postischemic ventricular dysfunction and reduce the incidence of ventricular arrhythmias. Tocotrienol-rich fraction was shown to stabilize 20S and 26S proteosome activities and reduce the ischemia-reperfusioninduced increase in c-Src phosphorylation (Das et al 2005). Esterhuyse et al investigated the effects of red palm oil enriched with tocotrienols and tocopherols on the myocardial nitric oxide-cGMP signaling pathway (Esterhuyse et al 2005).…”

Section: Anti-ischemic Property Of Tocotrienols In Cardioprotectionmentioning

confidence: 99%

Multifaceted role of tocotrienols in cardioprotection supports their structure: function relation

2011

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Tocotrienols are a class of vitamin E which modulates several mechanisms associated with cardioprotection, anti-cancer, anti-diabetic, and neuroprotection. Unlike other Vitamin E-like compounds, tocotrienols possess inimitable properties. Quite a lot of studies have determined the cardioprotective abilities of tocotrienols and have been shown to possess novel hypocholesterolemic effects together with an ability to reduce the atherogenic apolipoprotein and lipoprotein plasma levels. In addition, tocotrienol has been suggested to have an antioxidant, anti-thrombotic, and antitumor effect indicating that tocotrienol may serve as an effective agent in the prevention and/or treatment of cardiovascular disease and cancer. The bioactivity exhibited is due to the structural characteristics of tocotrienols. Rich sources of tocotrienols which include rice bran, palm oil, and other edible oils exhibit protective effect against cardiovascular disorders. The conclusions drawn from the early literature that vitamin E group of compounds provides an inevitable role in cardioprotection is sustained in many more recent studies.

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Cardioprotection with palm tocotrienol: antioxidant activity of tocotrienol is linked with its ability to stabilize proteasomes

Cited by 72 publications

References 36 publications

γ-Tocotrienol Promotes TRAIL-Induced Apoptosis through Reactive Oxygen Species/Extracellular Signal-Regulated Kinase/p53–Mediated Upregulation of Death Receptors

γ-Tocotrienol Promotes TRAIL-Induced Apoptosis through Reactive Oxygen Species/Extracellular Signal-Regulated Kinase/p53–Mediated Upregulation of Death Receptors

Cardioprotection with palm oil tocotrienols: comparision of different isomers

Multifaceted role of tocotrienols in cardioprotection supports their structure: function relation

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