Gamma-tocotrienol acts as a BH3 mimetic to induce apoptosis in neuroblastoma SH-SY5Y cells

Tan, Jen Kit; Then, Sue Mian; Mazlan, Musalmah; Rahman, Raja Noor Zaliha Raja Abdul; Jamal, A. Rahman A.; Ngah, Wan Zurinah Wan

doi:10.1016/j.jnutbio.2015.12.019

Cited by 14 publications

(10 citation statements)

References 63 publications

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“…Secondly, T3 may act differently when exist in combination with other compounds due to drug interaction. For instance, γT3 interferes with the generation of ROS by BSO which is beneficial for cancer cell death [399].…”

Section: Effects Of Tocotrienol On Cancersmentioning

confidence: 99%

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

et al. 2020

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Tocotrienol (T3) is a subfamily of vitamin E known for its wide array of medicinal properties. This review aimed to summarize the health benefits of T3, particularly in prevention or treatment of non-communicable diseases (NCDs), including cardiovascular, musculoskeletal, metabolic, gastric, and skin disorders, as well as cancers. Studies showed that T3 could prevent various NCDs, by suppressing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in the mevalonate pathway, inflammatory response, oxidative stress, and alternating hormones. The efficacy of T3 in preventing/treating these NCDs is similar or greater compared to tocopherol (TF). TF may lower the efficacy of T3 because the efficacy of the combination of TF and T3 was lower than T3 alone in some studies. Data investigating the effects of T3 on osteoporosis, arthritis, and peptic ulcers in human are limited. The positive outcomes of T3 treatment obtained from the preclinical studies warrant further validation from clinical trials.Nutrients 2020, 12, 259 2 of 84 Nutrients 2020, 12, 259 4 of 84 the order δ > γ > β > α [45]. Using HepG2 cells, γT3 was shown to stimulate apolipoprotein B (Apo-B) degradation by decreasing its translocation into the endoplasmic reticulum (ER) lumen. This action eventually caused a reduction in the number of Apo-B in lipoprotein particles [46]. Other reports showed that γT3 and δT3 had the potential to reduce the hepatic TG synthesis and very-low-density lipoprotein (VLDL) secretion by suppressing expression of genes involved in lipid homeostasis, particularly the TG, cholesterol, and VLDL biosynthesis. Moreover, δT3 also promoted the efflux of LDL through LDL receptor expression [47]. A summary of the literature on effect of T3 supplementation on lipid profile of hypercholesterolemic model in vitro is shown in Table 1.Animal models of dyslipidemia have been used to investigate the effects of T3 on lipid profile. Several animals have been tested, including chicken, swine and rodents (rats, hamsters, guinea pigs). In chickens fed with a varying level of αTF and γT3, Qureshi et al. (1996) showed that αTF enhanced the inhibition of HMGCR by γT3. They further stipulated that the vitamin E mixture should contain 15-20% of αTF and approximately 60% of γT3 or δT3 for optimal anti-cholesterol effects [48]. In the subsequent study, demonstrated that combination of 50 ppm T3-rich fraction (TRF) and 50 ppm lovastatin was more effective in suppressing HMGCR activity compared to lovastatin alone in chickens. The combination also reduced serum TC and LDL-C, TG, Apo-B, thromboxane B 2 , and platelet factor 4 in contrast to individual treatment [49]. Using chicken supplemented with 50 ppm of δT3, Qureshi et al. (2011) further revealed that δT3 reduced TC and LDL-C besides suppressing the lipid elevating effects of dexamethasone and potentiated the TG-lowering effect of riboflavin [50]. Using genetically hypercholesterolemic swine, Qureshi et al. (1991) demonstrated the significant effect of TRF in lowering serum TC, LDL-C, Apo-B, thrombo...

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Section: Effects Of Tocotrienol On Cancersmentioning

confidence: 99%

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

et al. 2020

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“…The TRMC consisted of α-tocotrienol, β-tocotrienol, and γ-tocotrienol and the δ-tocotrienol isomers. Some studies have shown that γ-tocotrienol induced apoptosis in neuroblastoma SH-SY5Y cells 47 and human gastric cancer cells. 48 In our previous study, we clearly showed that delta-tocotrienol induced apoptosis in NSCLC in a dose-and time-dependent manner at 10-30 µM concentrations.…”

mentioning

confidence: 99%

Tocotrienol-rich mixture inhibits cell proliferation and induces apoptosis via down-regulation of the Notch-1/NF-κB pathways in NSCLC cells

Rajasinghe¹,

Gupta²

2017

NDS

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Abstract:Lung cancer is one of the leading causes of cancer deaths. Non-small cell lung cancer (NSCLC), with a 5-year survival rate of 5% at stage IIIB, accounts for 80%-85% of all lung cancers. Aberrant Notch-1 expressions have been reported in lung cancer patients and could potentially be a beneficial molecular/therapeutic target against NSCLC. Tocotrienols, isomers of vitamin E, have been shown to exhibit antitumor activity via inhibition of different signaling pathways in tumor cells. Previously, we reported that delta-tocotrienol downregulates Notch-1 via NF-κB. However, the pure isomers are presently not available in quantities required for animal or clinical studies. Therefore, the objective of this study was to investigate the interactions and effects of commercially available tocotrienols (a mixture of isomers) on the Notch-1 pathway in NSCLC, adenocarcinoma (A549) and squamous cell lung cancer (H520) cell lines. A dose-dependent decrease in all growth, cell migration, and tumor invasiveness was observed in both cancer cell lines with the addition of tocotrienols. A significant induction of apoptosis was also observed using Annexin V stain in flow cytometry analysis. Since tocotrienols significantly affected proliferation, apoptosis, migration, and invasiveness, reverse transcription polymerase chain reaction and Western blot analysis were used to explore the molecular mechanisms responsible for the regulations by testing the expression of Notch-1 and its downstream genes. A dose-dependent decrease in expression of proteins was observed in Notch-1, Hes-1, Survivin, and Bcl-XL. In addition, we found a mechanism linking the NF-κB pathway and Notch-1 down-regulation from NF-κB DNA-binding activities. Thus, our data suggest that commercially available tocotrienols inhibits cell growth, migration, and tumor cell invasiveness via downregulation of Notch 1 and NF-κB while inducing apoptosis. Hence, these commercially available tocotrienol-rich mixture could potentially be an effective supplementation for lung cancer prevention.

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“…Tocotrienols have cytotoxic properties against cancer cells in culture (83–87). Many molecular mechanisms have been proposed, including induction of the mitochondrial apoptosis pathway (88,89), altered sphingolipid metabolism (90), endoplasmic reticulum stress (91), inhibition of telomerase (92), inhibition of signaling pathways involved in cytoskeletal organization (93) induction of cyclin dependent kinase inhibitors p21 and p27 (94), inhibition of canonical Wnt signaling (95), and modification of the Ras-ERK pathway (96).…”

Section: Tocotrienols Have Anti-cancer Propertiesmentioning

confidence: 99%

Utilization of Vitamin E Analogs to Protect Normal Tissues While Enhancing Antitumor Effects

Aykin-Burns

Pathak

Boerma

et al. 2019

Seminars in Radiation Oncology

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Despite advances in radiation delivery techniques, side effects of radiation therapy due to radiation exposure of normal tissues are common and can limit the deliverable dose to tumors. Significant interests lie in pharmacological modifiers that may protect against normal tissue toxicity from cancer treatment while simultaneously enhancing the tumor response to therapy. While no such treatments are available in the clinic, this is an area of active pre-clinical and clinical research. This review summarizes research studies that provide evidence to indicate that tocotrienols, natural forms of vitamin E, are potent radiation protectors and may also have anti-tumor effects. Hence, several current clinical trials test tocotrienols as concomitant treatment in cancer therapies.

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Gamma-tocotrienol acts as a BH3 mimetic to induce apoptosis in neuroblastoma SH-SY5Y cells

Cited by 14 publications

References 63 publications

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

Tocotrienol-rich mixture inhibits cell proliferation and induces apoptosis via down-regulation of the Notch-1/NF-κB pathways in NSCLC cells

Utilization of Vitamin E Analogs to Protect Normal Tissues While Enhancing Antitumor Effects

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Gamma-tocotrienol acts as a BH3 mimetic to induce apoptosis in neuroblastoma SH-SY5Y cells

Cited by 14 publications

References 63 publications

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

Tocotrienol-rich mixture inhibits cell proliferation and induces apoptosis via down-regulation of the Notch-1/NF-&kappa;B pathways in NSCLC cells

Utilization of Vitamin E Analogs to Protect Normal Tissues While Enhancing Antitumor Effects

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Tocotrienol-rich mixture inhibits cell proliferation and induces apoptosis via down-regulation of the Notch-1/NF-κB pathways in NSCLC cells