Gamma-tocotrienol treatment increased peroxiredoxin-4 expression in HepG2 liver cancer cell line

Sazli, Farahani Abdul Rahman; Jubri, Zakiah; Rahman, Mariati Abdul; Karsani, Saiful Anuar; Top, Abdul Gapor Md; Ngah, Wan Zurinah Wan

doi:10.1186/s12906-015-0590-y

Cited by 19 publications

(11 citation statements)

References 37 publications

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“…The anti-neoplastic effects of T3 have been extensively studied using tumor cells of mammary gland [351][352][353][354][355][356], lung [357][358][359][360][361][362], liver [363][364][365][366][367] pancreas [368], prostate [362,[369][370][371][372], cervix [373,374], skin [362,[375][376][377], brain [357][358][359]378], stomach [379], and colon [378,380]. Besides that, T3 tends to accumulate in the liver and pancreatic tissues as well as tumor tissues with an unknown mechanism [367,381].…”

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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“…It is time and dosedependent inhibition, therefore tocotrienol homologs show very high toxic or no effects. Previous studies by Aida et al (2007) and Sazli et al (2015) investigated the antiproliferative effects of gamma-T3 in HepG 2 , however, the authors used different treatment conditions (48-hour gamma-T3 treatment) and a higher gamma-T3 dose (170 mM and 70 mM respectively). showed that beta-, gamma-and delta-T3 significantly suppressed the proliferation of human hepatoma cells at concentrations higher than 20 mM for a 24-hour treatment.…”

Section: Resultsmentioning

confidence: 99%

Studies on the growth inhibiting and non-cytotoxic effects of tocotrienols on selected cancer cell lines

Szulczewska-Remi

Nogala‐Kałucka

2020

Acta Sci Pol Technol Aliment

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Background. Tocotrienols found in certain plant oils, like palm, rice bran, grapeseed and annatto seeds, have been reported to possess beneficial properties for humans, including cancer prevention. Since studies on their beneficial effects on human breast cancer cells have been extensively reviewed, the current understanding of how tocotrienols affect other cancer cells deserves further research. Therefore, the aim of this study was to investigate the antiproliferative and non-cytotoxic effects of tocotrienols on human hepatoma HepG 2 and colon colorectal Caco-2 cell cultures. Materials and methods. The cells were exposed to alpha-, beta-, gamma-or delta-tocotrienols at various concentrations and the antiproliferative activities were measured using MTS-based CellTiter 96 followed by a methylene blue assay for counting cells to evaluate the potential toxicity.Results. The research on HepG 2 showed statistically similar cytotoxic effects for both beta-and delta-T3 with no effects for alpha-and gamma-T3. Promising results were found for alpha-, beta-and gamma-T3 against CaCo-2. Conclusion.The exact reasons for the sensitivity of liver cancer cells to tocotrienols are unknown. Inhibition is time and dose-dependent, therefore tocotrienols' homologs show very high toxic or no effects. Tocotrienols appeared to be effective against colon cancer cells. Still, future investigation is necessary to explain the different mechanism of actions to support the antiproliferative effects of these homologs against colon cancer cells.

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“…The potency of tocotrienol isoforms against HCC cells were regarded as delta-tocotrienol > beta-tocotrienol > alpha-tocotrienol > gamma-tocotrienol [111,120]. Gamma-tocotrienol was thought to suppress the proliferation of HCC cells by overexpression of peroxiredoxin-4 (Prx4) [105]. Moreover, in HCC, gamma-tocotrienol intervention resulted in increased expression of Bax, caspase-8 and caspase-9; raising Bid fragmentation; suppressing STAT3 and its associated proteins such as Bcl-2, Bcl-xL, survivin, cyclin D1, Mcl-1, and VEGF.…”

Section: Tocotrienols In Liver Cancermentioning

confidence: 99%

Palm Oil Tocotrienols in Cancer Chemoprevention and Treatment

Abdullah¹,

Atia²,

Alrawaiq³

et al. 2022

Elaeis Guineensis

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Cancer remains a worrying cause of fatality worldwide despite the advancement in medicine. Among the dietary phytonutrients, tocotrienols have been extensively studied for their bioactivity against cancer. Palm oil is a rich source of tocotrienols. The most common formulation of tocotrienols is the tocotrienol-rich fraction of palm oil (TRF). The anticancer activities of tocotrienols were once presumed due to their antioxidant and free radical scavenging properties. However, recent evidence suggested that tocotrienols are capable of demonstrating cancer-fighting properties through their influence in various signalling pathways. The selectivity of tocotrienols in killing cancer cells without affecting normal cells is indicative of their potential role in cancer treatment and prevention. Tocotrienols had proven to be particularly effective in the chemoprevention and treatment of breast, colorectal, pancreatic, prostate and liver cancers in many in vitro and in vivo animal experiments. However, the efficacy of tocotrienols in the management of human cancers are still questionable due to their poor bioavailability and lack of well-designed clinical trials. Nevertheless, due to their superb safety profiles, palm oil tocotrienols are still considered ideal candidates for future large scale clinical trials to prove their efficacy to treat or prevent cancers in humans.

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Gamma-tocotrienol treatment increased peroxiredoxin-4 expression in HepG2 liver cancer cell line

Cited by 19 publications

References 37 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

Studies on the growth inhibiting and non-cytotoxic effects of tocotrienols on selected cancer cell lines

Palm Oil Tocotrienols in Cancer Chemoprevention and Treatment

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