Potential role of tocotrienols in the treatment and prevention of breast cancer

Sylvester, Paul W.; Akl, Mohamed R.; Malaviya, Abhita; Parajuli, Parash; Ananthula, Suryatheja; Tiwari, Roshan V.; Ayoub, Nehad M.

doi:10.1002/biof.1116

Cited by 47 publications

(41 citation statements)

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“…Tocotrienols are isomers of vitamin E, located primarily in plants, with antioxidative (9), anti-tumor (10) and neuroprotective functions (11). Tocotrienols inhibit proliferation of breast cancer cells, show G1 phase retardation and can promote cell apoptosis (12,13). However, to the best of our knowledge, the potential protective effect and underlying molecular mechanism of tocotrienol on SCI has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Tocotrienol alleviates inflammation and oxidative stress in a rat model of spinal cord injury via suppression of transforming growth factor-β

Xun

Mamat

Guo

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. In recent years accumulating evidence has indicated that tocotrienol exhibits an oxidation resistance function, decreased cholesterol function, inhibits cancer function and has unique physiological functions, including anti-inflammatory, anti-apoptotic and anti-oxidative properties. The present study investigated the effect of tocotrienols on spinal cord injury (SCI) by evaluating oxidative stress, inflammation and inducible nitric oxide synthase (iNOS) in rats. A rat model of SCI was induced by operation. SCI rats were treated with 120 mg/kg/day tocotrienol once a day for eight consecutive weeks. Functional recovery following SCI was measured by using the Basso Beattie Bresnahan (BBB) locomotor rating scale. Then the volume of spinal cord contusions was measured following induction of SCI in the rats. In SCI rats, serum malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, nuclear factor-κB p65 unit, tumor necrosis factor-α, interleukin (IL)-1β and IL-6 levels were analyzed using respective commercial immunoassay kits. Firstly, iNOS, transforming growth factor (TGF)-β, collagen type IV and fibronectin protein expression levels, in addition to iNOS activity and plasma nitric oxide (NO) production in SCI rats was analyzed using western blot analysis, commercial kits and Griess reagent, respectively. Tocotrienol treatment elevated BBB scores and contused volume in the SCI rats. Tocotrienol protected against SCI with reduced oxidative stress and inflammation, and inhibited iNOS protein expression iNOS activity and plasma NO production in rats. In addition, treatment with tocotrienols suppressed TGF-β, collagen type IV and fibronectin protein expression levels in SCI rats. These results suggest that tocotrienols protect SCI, and suppress oxidative stress, inflammation and iNOS in this model of SCI through TGF-β, collagen type IV and fibronectin signaling pathways.

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Section: Introductionmentioning

confidence: 99%

Tocotrienol alleviates inflammation and oxidative stress in a rat model of spinal cord injury via suppression of transforming growth factor-β

Xun

Mamat

Guo

et al. 2017

Experimental and Therapeutic Medicine

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“…38,39) A great deal of evidence indicates that the anticancer activity of γ-tocotrienol is mediated, at least in part, by its accumulation and disruption of lipid raft integrity and suppression of receptor activation and signaling. 25) Specifically, studies have shown that breast cancer cells exposed to growth inhibiting doses of γ-tocotrienol display significant inhibition in HER2/ErbB2, HER3/ErbB3, HER4/ErbB4, and c-Met activation, [25][26][27]37,[40][41][42] and their downstream effectors including mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt, Stat, and nuclear factorkappa B (NFκB).…”

Section: Discussionmentioning

confidence: 99%

Role of Rac1/WAVE2 Signaling in Mediating the Inhibitory Effects of γ-Tocotrienol on Mammary Cancer Cell Migration and Invasion

Algayadh

Dronamraju

Sylvester

2016

Biological & Pharmaceutical Bulletin

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The majority of breast cancer deaths result from the progression of this disease to a metastatic phenotype. Rac1 and Cdc42 are Rho family members that together with their downstream effectors, Wiskott-Aldrich Syndrome protein-family verprolin-homologous protein 2 (WAVE2) and Arp2/3, play an important role in cytoskeletal reorganization and the formation of membrane protrusions that promote cancer cell migration and invasion. γ-Tocotrienol, is a natural isoform within the vitamin E family of compounds that inhibits breast cancer cell growth and progression by suppressing various signaling pathways involved in mitogenic signaling and metastatic progression. Studies were conducted to examine the effects of γ-tocotrienol on Rac1/WAVE2 signaling dependent migration and invasion in highly metastatic mouse SA and human MDA-MB-231 mammary cancer cells. Exposure to γ-tocotrienol resulted in a dose-responsive decrease in Rac1/WAVE2 signaling as characterized by a suppression in the levels of Rac1/Cdc42, phospho-Rac1/Cdc42, WAVE2, Arp2, and Arp3 expression. Additional studies also demonstrated that similar treatment with γ-tocotrienol resulted in a significant reduction in tumor cell migration and invasion. Taken together, these findings indicate that γ-tocotrienol treatment effectively inhibits Rac1/WAVE2 signaling and reduces metastatic phenotypic expression in mammary cancer cells, suggesting that γ-tocotrienol may provide some benefit as a novel therapeutic approach in the treatment of metastatic breast cancer.Key words γ-tocotrienol; breast cancer; Rac1; Wiskott-Aldrich Syndrome protein-family verprolin-homologous protein 2 (WAVE2); migration; invasion Breast cancer is the most common form of cancer in women and is second only to lung cancer as a leading cause of cancer mortality in the United States.1,2) The vast majority of breast cancer deaths result from the development and progression of the metastatic form of this disease, that is characterized by cancer cells detaching from the primary tumor and spreading to distant sites in the body such as the bone, brain, surrounding lymph nodes, liver, and lungs.3-5) Breast cancer metastasis is a complex and multistep process that includes morphological changes, detachment from the basement membrane, increased mobility and invasion into surrounding tissues, intravasation, circulation, adhesion, extravasation, and growth at distant sites. 6) Since patient prognosis for metastatic breast cancer is very poor, there is great interest in developing antiinvasion therapies to improve patient treatment and survival. 7)An initial step in the metastasis process involves epithelialto-mesenchymal transition (EMT), where neoplastic epithelial cells lose their cellular polarity and acquire mesenchymal-like mobility that allows them to invade surrounding tissues. [8][9][10][11] This amoeboid-like movement requires the formation of cellular protrusions that result from the conversion of monomeric globular actin (G-actin) to polymerized filamentous actin (Factin). 12-15)The Rho family of sm...

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“…γ-tocotrienol also works in colon cancer cells synergistically with atorvastatin when tested in vitro [46,47]. This combination decreased the RhoA protein concentration in the cell membrane by inhibiting the geranylgeranylation of RhoA and caused cell cycle arrest.…”

Section: Statins With γ-Tocotrienolmentioning

confidence: 99%