Serving as an important driver in the canonical pathway, the activation of Wnt receptors leads to translocation of -catenin into nucleus. Taken together, the ability of tocotrienols in targeting Wnt pathway suggests a value-added therapy to effectively regulate proliferation, apoptosis, and metastasis simultaneously. It transduces a downstream signaling cascade to the effector caspase (caspase-8), leading to the proteolytic activation of caspase-3. Anti-proliferative effects of gamma-tocotrienol are associated with suppression of c-Myc expression in mammary tumour cells. The distinction between tocotrienols and tocopherols is chemical. Malignancy often arises from sophisticated defects in the intricate molecular mechanisms of cells, rendering a complicated molecular ground to effectively target cancers. Theres little research on topical application of tocotrienols, but what researchers know so far suggests its safe to apply tocotrienol-infused products to the skin. Jerantinine A induces tumor-specific cell death through modulation of splicing factor 3b subunit 1 (SF3B1). Ahsan H., Ahad A., Iqbal J., Siddiqui W.A. The ATF6 pathway of the ER stress response contributes to enhanced viability in glioblastoma. Sakai M., Okabe M., Tachibana H., Yamada K. Apoptosis induction by gamma-tocotrienol in human hepatoma Hep3B cells. Investigating the power of music for dementia. Learn more about the risk factors and, Oranges may help lower the risk of stroke, support the heart and skin, and aid diabetes management. Bioavailability of tocotrienols: Evidence in human studies. Vaquero E.C., Rickmann M., Molero X. Tocotrienols balancing the mitochondrial crosstalk between apoptosis and autophagy tocotrienols induce apoptosis and autophagy in rat pancreatic stellate cells through the mitochondrial death pathway. alpha, beta, gamma and delta. drafted parts of the content in Section 6. S.-Y.T. Because it causes few or no side effects, it is safe for most people to try. Considering that apoptotic products are closely related to NF-B activity, agents that can reduce the NF-B level could serve as a potential multitasking agent. In addition to serving as a powerhouse for fueling energy to cells, this organelle also contains homicidal molecules that can subject a cell to death [49]. Gamma-tocotrienol inhibits pancreatic tumors and sensitizes them to gemcitabine treatment by modulating the inflammatory microenvironment. . The activated pancreatic stellate cells treated with TRF exhibit the ability of tocotrienols to co-induce mitochondria-mediated apoptosis and autophagy [53]. -T3-enriched diet suppressed COX-2 protein levels in colorectal mucosa. EGR-1/Bax pathway plays a role in vitamin E -tocotrienol-induced apoptosis in pancreatic cancer cells. -Tocotrienol suppresses growth and sensitises human colorectal tumours to capecitabine in a nude mouse xenograft model by down-regulating multiple molecules. In an attempt to study the underlying molecular mechanism, a specific estrogen receptor inhibitor (fulvestrant) employed as a competitive inhibitor to tocotrienols showed a reduction in the expression of proapoptotic genes [70]. Zhan T., Rindtorff N., Boutros M. Wnt signaling in cancer. The resultant apoptosis was evident by caspase-7 activation and PARP cleavage. Rasol N.E., Ahmad F.B., Lim X.Y., Chung F.F.L., Leong C.O., Mai C.W., Bihud N.V., Zaki H.M., Ismail N.H. Cytotoxic lactam and naphthoquinone alkaloids from roots of Goniothalamus lanceolatus Miq. Mebratu Y., Tesfaigzi Y. government site. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (. Viola V., Ciffolilli S., Legnaioli S., Piroddi M., Betti M., Mazzini F., Pierpaoli E., Provinciali M., Galli F. Mitochondrial-dependent anticancer activity of -tocotrienol and its synthetic derivatives in HER-2/neu overexpressing breast adenocarcinoma cells. 2015;8(2):45-59. Cudraflavone C induces tumor-specific apoptosis in colorectal cancer cells through inhibition of the phosphoinositide 3-Kinase (PI3K)-AKT Pathway. They exist in four isomeric forms, namely, alpha ()-, beta ()-, gamma ()-, and delta ()-T3, which are distinguished by the position and number of methyl groups in the chromanal head. Rajendran P., Li F., Manu K.A., Shanmugam M.K., Loo S.Y., Kumar A.P., Sethi G. -Tocotrienol is a novel inhibitor of constitutive and inducible STAT3 signalling pathway in human hepatocellular carcinoma: Potential role as an antiproliferative, pro-apoptotic and chemosensitizing agent. Rajasinghe L.D., Gupta S.V. Bray F., Ferlay J., Soerjamataram I., Siegel R.L., Torrer L.A., Jemal A. Ji X., Wang Z., Sarkar F.H., Gupta S.V. -T3 downregulated NF-B and NF-B-regulated cyclin D1, COX-2, survivin, Bcl-xL, XIAP, ICAM-1, MMP-9 and VEGF. Nicotine use can cause osteoporosis, but research has found that tocotrienol lowers the risk. Furthermore, another clinical study investigating the new formulation of --T3 showed an enhanced bioavailability in healthy subjects ({"type":"clinical-trial","attrs":{"text":"NCT01571921","term_id":"NCT01571921"}}NCT01571921), undoubtedly heralding a great milestone for accelerating its application for cancer therapy. Taken together, these studies could provide a better understanding on clinical applications of tocotrienols with optimal benefits. Here, our viscosity-adapted -T3 NE platform was developed to additionally incorporate curcumin (CUR Vitamin E -tocotrienol augments the antitumor activity of gemcitabine and suppresses constitutive NF-kB activation in pancreatic cancer. Some cosmetic and skin care product manufacturers include both tocopherol and tocotrienol in their vitamin E products. The endogenous LC3-I, present in the cytoplasm, is processed to LC3-II and bound to the autophagosome during autophagy. Tocotrienols are chemicals in the vitamin E family. As a result, the blocking of NF-B pathway leads to the suppression of antiapoptotic gene products and potentiation of apoptosis [92]. Pharmacological potential of tocotrienols: A review. The application of salubrinal (inhibitor of ER stress) has been found to successfully block the cytotoxicity of -T3, signifying the importance of ER stress for apoptosis induction [71]. Chang P.N., Yap W.N., Lee D.T., Ling M.T., Wong Y.C., Yap Y.L. Tocotrienols have been previously reported to concurrently activate cell death programs and downregulate prosurvival signaling pathways, such as nuclear factor kappa B (NF-B), phosphoinositide 3-kinase (PI3K)/Akt, Wingless and INT-1 (Wnt), and mitogen-activated protein kinases (MAPKs) (Figure 6). Prolonged survival and delayed progression of pancreatic intraepithelial neoplasia in LSL-Kras; Pdx-1-Cre mice by vitamin E -tocotrienol. Komar H.M., Serpa G., Kerscher C., Schwoegl E., Mace T.A., Jin M., Yang M.C., Chen C.S., Bloomston M., Ostrowski M.C., et al. and transmitted securely. Unlike other forms of vitamin E, tocotrienols are less commonly found in nature. Kabir M.I., Adnan M., Rahman M.M. For instance, translocation of ERK1/2 to nucleus carries an anticancer role, while positioning to mitochondria may promote cell survival [110]. Gamma-tocotrienol promotes TRAIL-induced apoptosis through reactive oxygen species/extracellular signal-regulated kinase/p53-mediated upregulation of death receptors. Sui X., Kong N., Ye L., Han W., Zhou J., Zhang Q., He C., Pan H. JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents. . However, metabolism, toxicities, and pharmacokinetics studies of combined treatments in vivo are still lacking, more investigations are therefore necessary to advance effective drug combinations toward a tangible clinical application in the near future. However, like with any skincare product, theres a potential for skin irritation. You can also take tocotrienol in supplement form. Accessibility An official website of the United States government. 2.79, 1.55 and 0.44 g/mL for -, - and -tocotrienol . Although a reduction of ATF6 level has been observed in +SA cells, the spatial information in relation to its cleavage has not been studied [68]. Studies of rats have found that tocotrienol may slow the course of free radical-related bone loss. Labi V., Erlacher M. How cell death shapes cancer. Food sources include liver, carrots, and green, leafy vegetables. Specifically, interventions of tocotrienols are involved as neoadjuvant and adjuvant cancer treatments as well as health supplements [129]. Yap W.N., Chang P.N., Han H.Y., Lee D.T., Ling M.T., Wong Y.C., Yap Y.L. Tiwari R.V., Parajuli P., Sylvester P.W. Abubakar I.B., Lim K.H., Kam T.S., Loh H.S. Polymer-conjugated tocotrienols [119] and entrapment of tocotrienols in nanovesicles [120] have been investigated for intravenous injection, while tocotrienol nanoemulsions have been investigated for topical applications [121]. In addition to tocotrienols inducing apoptosis via intrinsic mitochondrial pathway, a few studies have shown that both intrinsic and extrinsic pathways are activated concurrently. Subjects were given either two 300 mg GDT (450 mg -T3 and 150 mg -T3) capsules or four 200 mg TRF (451.2 mg -T3 & 102.72 mg -T3) capsules and blood samples were taken at several time points. -T3 inhibited the growth and progression of melanoma xenografts in nude mice. However, it will be more worthwhile if -T3, which is claimed to serve as an inhibitor of antiapoptotic Bcl-2 members, can be further characterized to allow development of derivatives that embrace a greater therapeutic efficacy [57]. Vitamin E (VE) tocotrienols (T3), recognized for their cancer-specific anti-proliferative and pro-apoptotic activities, have been previously fabricated into bio-active nanoemulsion (NE) formulations. Apoptosis gene network regulated by delta-tocotrienol in K562 chronic myeloid leukemia cells. This figure is expected to increase continuously due to a high prevalence of cancer cases in aged population [2]. The possible mechanism of action of palm oil -tocotrienol and -tocopherol on the cervical carcinoma CaSki cell apoptosis. In fact, MOMP is a critical event in the intrinsic apoptotic pathway. Experimental study on delta-tocotrienol inhibits the Wnt pathway in the colon cancer cell SW620. De Silva L., Chuah L.H., Meganathan P., Fu J.Y. Research has also found that tocotrienols play a role in fighting liver, colon, prostate, lung, stomach, skin, and pancreatic cancers. Tocotrienols arent easy to find in supplement form. It is possible that tocotrienols-induced ER stress is rapid and favors apoptosis, leaving behind the prosurvival option. Biochemical. Delta-tocotrienol augments cisplatin-induced suppression of non-small cell lung cancer cells via inhibition of the Notch-1 pathway. The stimuli then perceive cell death signals via the mitochondrion, which represents the metabolic status of a cell. Abbreviations: ABCG2, ATP-binding cassette subfamily G member 2; Akt, or PKB, protein kinase B; ATF, activating transcription factor; ATP, adenosine triphosphate; Bcl-xL, B-cell lymphoma-extra large; BiP, or GRP78, glucose-regulated protein; CDK, cyclin-dependent kinase; CHOP, CCAAT-enhancer-binding protein homologous protein; cIAP, cellular inhibitor of apoptosis; COX-2, cyclooxygenase-2; CXCR4, C-X-C motif chemokine receptor 4; DR, death receptor; EGR, early growth response; eIF2-, eukaryotic initiation factor 2 alpha; ERK1/2, extracellular signal-regulated protein kinases 1 and 2; ERO1, endoplasmic reticulum oxidation 1; ETK1, epithelial and endothelial tyrosine kinase; FDFT1, farnesyl-diphosphate farnesyltransferase 1; GSK-, glycogen synthase kinase 3 beta; Hes-1, hairy and enhancer of split-1; hTERT, human telomerase reverse transcriptase; ICAM-1, intercellular adhesion molecules-1; Id-1, inhibitor of differentiation/DNA binding; IB/, inhibitor of kappa B alpha/beta; IKK/, IB kinase alpha/beta; IL-6, interleukin 6; IRE-1, inositol-requiring enzyme 1; JNK, c-Jun N-terminal kinase; LC3, microtubule-associated protein 1A/1B-light chain 3; MC1R, melanocortin 1 receptor; Mcl-1, myeloid cell leukemia 1; MEK, mitogen-activated protein kinase; MIC-1, macrophage inhibitory cytokine 1; MITF, melanogenesis associated transcription factor; MMP, matrix metalloproteinases; mTOR, mammalian target of rapamycin; NF-B, nuclear factor kappa B; Oct-4, octamer-binding transcription factor 4; p27Kip1, cyclin-dependent kinase inhibitor 1B; PARP, poly(ADP-ribose) polymerase; PCNA, proliferating cell nuclear antigen; PERK, PKR-like ER-localized eIF2 kinase; PI3K, phosphoinositide 3-kinase; ROS, reactive oxygen species; SAPK/JNK, stress-activated protein kinase/c-Jun NH2-terminal kinase; Sox-2, sex determining region Y-box 2; TGF-1, transforming growth factor beta 1; TYRP, tyrosinase-related proteins; VEGF, vascular endothelial growth factor; uPA, urokinase-type plasminogen activator; Wnt, wingless/integrase; XBP, X-box binding protein; XIAP, X-linked inhibitor of apoptosis protein; -SMA, alpha-smooth muscle actin. That said, it's best to err on the side of caution and avoid taking too much. Its possible that cost comes into play. In particular, the potential of tocotrienols in inducing nonapoptotic cell death has not been well described and certainly deserves more research attention. In a study of rats that compared tocotrienol to tocopherol, tocotrienol alone stopped hormonal and acidity changes related to stress. Bax initiates MOMP to induce apoptosis, leading to generation of ROS, which serves as a second messenger to trigger the expression of autophagy-related protein (Atg). This is because there are more tocopherols in people's diets and some vitamin E. In the process of transforming healthy cells to cancer cells, the core changes include increased proliferation and decreased cell death [26]. Inhibition of NF-B by tocotrienols has been reported to reduce the expression of various proteins linked to cell survival, such as antiapoptosis (e.g., Bcl-2, Bcl-xL, cFLIP, IAP-1, IAP-2, XIAP, Bfl-1/A1, TRAF1, and survivin), proliferation (e.g., c-Myc and cyclin D1), inflammation (COX-2, cytokines), invasion (e.g., MMP-9, ICAM-1, ELAM-1, and VCAM-1), and neoangiogenesis (e.g., VEGF) [92,93,94]. Biological properties of tocotrienols: Evidence in human dtudies. TRF suppressed the growth of human colon cancer xenografts in Balb/c nude mice via the Wnt pathway, by which the expressions of -catenin, Wnt, and c-Myc proteins in xenografts were significantly downregulated [23]. Cancer Chemother Pharmacol. There are three important MAPK members for maintenance of cells, namely, extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs), and p38-MAPKs. In comparison, the connection of ceramides with autophagy is emerging; the ceramides may activate c-Jun N-terminal 1 (JNK1) to phosphorylate Bcl-2 (inactivation), eventually leading to the dissociation of Beclin-1 from Bcl-2 [90]. Antiproliferation and induction of caspase-8-dependent mitochondria-mediated apoptosis by -tocotrienol in human lung and brain cancer cell lines. As with many other supplements, the primary risk is getting too much. We avoid using tertiary references. Gamma-tocotrienol inhibits neoplastic mammary epithelial cell proliferation by decreasing Akt and nuclear factor kappaB activity. National Library of Medicine Synergistic anticancer effects of combined -tocotrienol and oridonin treatment is associated with the induction of autophagy. Brentnall M., Rodriguez-Menocal L., De Guevara R.L., Cepero E., Boise L.H. Tocotrienols are a group of chemicals that are part of the vitamin E family. This, in theory, could prevent wrinkles and help the skin look appear youthful. Tocotrienols exhibit mitochondrial disruption capacity via mitochondrial outer membrane permeabilization (MOMP) induction [50,51,52], culminating in mitochondria-mediated apoptosis. Exemplar in vitro studies for elucidating the molecular targets of tocotrienols-induced cell death. Ultra moisturizing anti-wrinkle lotion enriched with tocotrienols [Abstract]. Of note, it has been proposed that the roles of p38 and JNK regulate the balance of apoptosis and autophagy in response to chemotherapeutic agents, portraying a significant role of MAPK signaling in deciding life or death matter. Free radicals are chemicals linked to a host of health issues, including skin aging, cancer, and numerous diseases. On the other hand, another study revealed that the elevated Bax expression induced by -T3 correlates to the induction of zinc finger transcription factor, known as early growth response protein 1 (EGR1). Inhibition of Jak/STAT signaling reduces the activation of pancreatic stellate cells in vitro and limits caerulein-induced chronic pancreatitis in vivo. Abubakar I.B., Lim K.H., Kam T.S., Loh H.S. Abbreviations: BiP or GRP78, glucose-regulated protein; CHOP, CCAAT-enhancer-binding protein homologous protein; PERK, PKR-like ER-localized eIF2 kinase; IRE1, inositol-requiring enzyme 1; ATF, activating transcription factor; eIF2-, eukaryotic initiation factor 2 alpha; Cas-, caspase-; PARP, poly(ADP-ribose) polymerase; sXBP1, spliced X-box binding protein 1, TRB3, tribbles 3. H.-S.L. Journal of Dispersion Science and Technology. Brigelius-Floh R. Induction of drug metabolizing enzymes by vitamin E. Chen D.H., Zhang X.S. Tocotrienols may help fight free radical damage to the gastrointestinal system. Eitsuka T., Nakagawa K., Miyazawa T. Down-regulation of telomerase activity in DLD-1 human colorectal adenocarcinoma cells by tocotrienol. Although statistically insignificant due to limited sample size, the first clinical study conducted on breast cancer patients showed that TRF in combination with tamoxifen improved breast-cancer-specific survival compared to the tamoxifen group ({"type":"clinical-trial","attrs":{"text":"NCT01157026","term_id":"NCT01157026"}}NCT01157026) [38]. 2023 Dotdash Media, Inc. All rights reserved, Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. -T3 has been reported to engage both intrinsic and extrinsic pathways in Hep3B human hepatoma cells, as demonstrated by elevated activities of caspase-8, -9, -3 and accompanied by upregulation of truncated Bid and Bax, resulting in PARP cleavage [45]. The natural form of vitamin E is composed of 4 different tocopherols and 4 different tocotrienol homologues (alpha . If you take a supplement and get plenty of vitamin E in your diet, you may be taking too much, even if youre taking the recommended dose on the supplement bottle. Share. Tocotrienols are less widely available in supplement form than other forms of vitamin E.. Fulda S., Debatin K.M. 2014;14(4):195-204. doi:10.17305/bjbms.2014.4.91, Aggarwal BB, Sundaram C, Prasad S, Kannappan R. Tocotrienols, the vitamin E of the 21st century: Its potential against cancer and other chronic diseases. Tocotrienols have been shown to reduce constitutive NF-B activity in mammary epithelial [95], prostate cancer [19], multiple myeloma [92], lung adenocarcinoma [96], oral cancer [97], and colon carcinoma [56] cell lines. In addition, -T3 inhibited cell viability through suppression of -catenin/TCF signaling in human colon carcinoma HT-29 cells [42]. -Tocotrienol induces apoptosis in human T cell lymphoma through activation of both intrinsic and extrinsic pathways. toward generating the paper as presented. Gamma-tocotrienol inhibits ErbB3-dependent PI3K/Akt mitogenic signalling in neoplastic mammary epithelial cells. Inoue A., Takitani K., Koh M., Kawakami C., Kuno T., Tamai H. Induction of apoptosis by -tocotrienol in human cancer cell lines and leukemic blasts from patients: Dependency on Bid, cytochrome c, and caspase pathway. So far, research has uncovered numerous benefits associated with tocotrienols. Dosage and Preparation What to Look For Other Questions Tocopherols are a family of compounds that together make up different forms of vitamin E. When you buy a supplement that's advertised as "mixed tocopherols," you're purchasing a mixture of several different types of vitamin E. The first clinical trial of tocotrienols in cancer patients was embarked in 2006. Sailo B.L., Banik K., Padmavathi G., Javadi M., Bordoloi D., Kunnumakkara A.B. Tocotrienols are a less common form of vitamin E than tocopherols. Tocotrienols can help prevent and reduce osteoporosis-related bone loss in several ways. Furthermore, combining existing drugs with tocotrienols could also serve as an immediate and cost-effective solution. Tocotrienols can also reduce the power of other cardiovascular health risk factors, including the impact of high cholesterol on heart health. Of note, -T3 and -T3 have been reported to exert most potent anticancer effects [17,18,19,20]. When youre shopping for a vitamin E supplement or a multivitamin that contains vitamin E, always check the dosage. In another study where tocotrienols were given at higher doses (296 mg -tocotrienol, 284 mg -tocotrienol and 83 mg -tocotrienol), the peak plasma concentrations of -tocotrienol did not seem to increase proportionally, i.e. Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a healthcare professional. : Kamal Patel, MPH, MBA Last Updated: September 28 2022 summary Dosage information Examine Database Research Feed Research breakdown References Summary Vitamin E is a term used to refer to eight molecules, which are divided into two categories: tocopherols and tocotrienols. Delta-tocotrienol inhibits non-small-cell lung cancer cell invasion via the inhibition of NF-B, uPA activator, and MMP-9. Selvaraju, T. R., Khaza'ai, H., Vidyadaran, S., Mutalib, M. S. A., & Vasudevan, R. (2014, November). Some studies suggest that applying tocotrienol to the skin may help, but the improvements are modest and more research is needed. The activation of extrinsic apoptotic pathway being coupled to ER stress suggests a close connection between them. Rickmann M., Vaquero E.C., Malagelada J.R., Molero X. Tocotrienols induce apoptosis and autophagy in rat pancreatic stellate cells through the mitochondrial death pathway. Loganathan R., Selvaduray K.R., Nesaretnam K., Radhakrishnan A.K. Advances in Experimental Medicine and Biology. For example, -T3 is predominantly higher in rice and palm compared to annatto, which mainly consists of -T3. Wali V.B., Bachawal S.V., Sylvester P.W. You can learn more about how we ensure our content is accurate and current by reading our. As a library, NLM provides access to scientific literature. Research into tocotrienols has thus far demonstrated their potential to be such an agent, with tocotrienols surpassing the pharmacological potential of tocopherols. Both traditional vitamin E in the form of tocopherol and the tocotrienol form of vitamin E offer similar benefits. Exhibiting cancer selectivity and exerting multitargeted actions for effectively killing various types of cancers, tocotrienols (T3) appear as a promising, novel anticancer candidate. Hodul P.J., Dong Y., Husain K., Pimiento J.M., Chen J., Zhang A., Francois R., Pledger W.J., Coppola D., Sebti S.M., et al. Our team thoroughly researches and evaluates the recommendations we make on our site. -T3 inhibited tumorigenicity of PC-3 cells in mice. Licensee MDPI, Basel, Switzerland. In addition, activation of both intrinsic and extrinsic pathways has been reported in leukemic cells, involving upregulation of genes in Bcl-2, caspases, and death receptor families [80]. Recent clinical trials conducted using tocotrienols for various cancer treatments. The process of autophagy. Shun M.C., Yu W., Gapor A., Parsons R., Atkinson J., Sanders B.G., Kline K. Pro-apoptotic mechanisms of action of a novel vitamin E analog (-TEA) and a naturally occurring form of vitamin E (-Tocotrienol) in MDA-MB-435 human breast cancer cells. Pharmacokinetics and safety of vitamin e -tocotrienol after single and multiple doses in healthy subjects with measurement of vitamin e metabolites. Of note, autophagy appears to account for a better role in cell death than its classical association in cell survival to serve as a backup mechanism in tocotrienols-induced apoptosis. Sylvester P.W., Ayoub N.M. Tocotrienols target PI3K/Akt signaling in anti-breast cancer therapy. In fact, engagement of both extrinsic and intrinsic apoptotic pathways by tocotrienols could lead to a more effective cancer elimination, particularly in Type II cells, which require mitochondrial pathway in inducing apoptosis. Nesaretnam K.S., Kanga R., Abdul-Razak G., Veerasenan S.D., Gomez P.A. El-Khattouti A., Selimovic D., Haikel Y., Hassan M. Crosstalk between apoptosis and autophagy: Molecular mechanisms and therapeutic strategies in cancer. Mai C.W., Kang Y.B., Pichika M.R. Like with most vitamins, your best bet is to get them through food sources. If you buy through links on this page, we may earn a small commission Heres our process. Taking higher amounts in supplement form may cause adverse effects. Later, concurrent activation of apoptosis and autophagy was correspondingly reported in other cancer cell lines, such as breast and prostate [86,87]. Miyazawa T., Shibata A., Nakagawa K., Tsuzuki T. Anti-angiogenic function of tocotrienol. Hence, considerable attention should be given to understand the tocotrienols-induced molecular crosstalk to gain insights on the cancer-specific mode of action. Dosing Reviews (2) Overview Vitamin E is an essential nutrient that includes both tocotrienols and tocopherols. Some research also suggests that tocotrienols may help fight Parkinsons disease or slow the course of the disease. Husain K., Centeno B.A., Chen D.T., Fulp W.J., Perez M., Lee G.Z., Luetteke N., Hingorani S.R., Sebti S.M., Malafa M.P. Tocotrienols exhibit versatility in inducing cell death by modulating various mechanisms in cancers. TRF has also been shown to exhibit apoptosis [21] and induce cell cycle arrest [22] and growth inhibition of human colon xenografts in nude mice [23]. Tocotrienols promote apoptosis in human breast cancer cells by inducing poly(ADP-ribose) polymerase cleavage and inhibiting nuclear factor kappa-B activity. The authors declare no conflict of interest. In prostate cancer cells, -T3 induced elevated intracellular ceramides (dihydrosphingosine and dihydroceramide), which appear to be potent mediators of apoptosis and autophagy [87]. In breast cancer cells, -T3 reversed the epithelial-to-mesenchymal transition in human breast cancer via the inhibition of canonical Wnt signaling [115]. Meganathan P., Fu J.Y. By Steph Coelho At normal doses, theres no evidence that tocotrienols interact with any drugs. Husain K., Francois R.A., Yamauchi T., Perez M., Sebti S.M., Malafa M.P. -T3 inhibited cancer cell proliferation and increased cleaved caspase-3. -T3 increased cleaved PARP and cleaved caspase-3. Effectiveness of tocotrienol-rich fraction combined with tamoxifen in the management of women with early breast cancer: A pilot clinical trial. As a result, proapoptotic molecules become available to permeabilize the outer mitochondrial membrane and release cytochrome c to the cytosol, leading to caspase-9- and caspase-3-dependent apoptosis [57]. Shin-Kang S., Ramsauer V.P., Lightner J., Chakraborty K., Stone W., Campbell S., Reddy S.A., Krishnan K. Tocotrienols inhibit AKT and ERK activation and suppress pancreatic cancer cell proliferation by suppressing the ErbB2 pathway. 8 High-Fat Foods for Your Diet, The 9 Best Vitamins and Supplements for Skin Health, The neuroprotective effects of tocotrienol rich fraction and alpha tocopherol against glutamate injury in astrocytes, Tocotrienols, the vitamin E of the 21st century: Its potential against cancer and other chronic diseases, Ultra moisturizing anti-wrinkle lotion enriched with tocotrienols, Effects of tocotrienol supplementation on hair growth in human volunteers, Vitamin E-drug interactions: Molecular basis and clinical relevance, A review of characterization of tocotrienols from plant oils and foods. Then, the lysosomal permeases and transporters export amino acids and other by-products of degradation back to the cytoplasm, where they can be reused for building macromolecules and for metabolism [37]. Thus, among the vitamin E isomers, -TP is the most common form found in human diets; it also has the highest bioavailability. Other than pure isomers, tocotrienol-rich fraction (TRF) is the most commonly available form of vitamin E oral supplement, containing a mixture of -, -, -T3, and some -tocopherol. Health effects A number of health benefits of tocotrienols have been proposed, included decreased risk of heart disease and cancer. However, scientists suggest that people interested in getting the most benefits from their vitamin E supplement should choose a supplement containing both tocopherols and tocotrienols. Podszun M, Frank J. Vitamin E-drug interactions: Molecular basis and clinical relevance. Ma Y., He N., Zhang J., Li D., Liu Y., Zhang J. Kannappan R., Ravindran J., Prasad S., Sung B., Yadav V.R., Reuter S., Chaturvedi M.M., Aggarwal B.B. using single dose tocotrienol-rich fractions (TRF) derived from palm oil [21-23]. Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis. Several recent reviews have comprehensively summarized the general biological effects of tocotrienols, including anti-inflammation, antihyperlipidemic, immunomodulation, neuroprotection, gastroprotection, hepatoprotection, nephroprotection, radioprotection, and anticancer [27,28,29].
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