Tocotrienols: The promising analogues of vitamin E for cancer therapeutics

Sailo, Bethsebie Lalduhsaki; Banik, Kishore; Padmavathi, Ganesan; Monisha, Javadi; Bordoloi, Devivasha; Kunnumakkara, Ajaikumar B.

doi:10.1016/j.phrs.2018.02.017

Cited by 113 publications

(88 citation statements)

References 162 publications

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“…24,41,42 In line with these data, the anti-cancer activity of TTs (specifically γ-and δ-TT) was reported in a wide range of tumours. 24,41,42 In line with these data, the anti-cancer activity of TTs (specifically γ-and δ-TT) was reported in a wide range of tumours.…”

Section: Discussionsupporting

confidence: 62%

“…24,36 Although most of the studies so far reported were performed with γ-TT, δ-TT was shown to be the most effective vitamin E isoform in triggering cell death in prostate cancer cells 37,38 ; however, the molecular mechanisms/targets of this activity are poorly clarified. 24,36 Although most of the studies so far reported were performed with γ-TT, δ-TT was shown to be the most effective vitamin E isoform in triggering cell death in prostate cancer cells 37,38 ; however, the molecular mechanisms/targets of this activity are poorly clarified.…”

Section: Discussionmentioning

confidence: 99%

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δ‐Tocotrienol induces apoptosis, involving endoplasmic reticulum stress and autophagy, and paraptosis in prostate cancer cells

et al. 2019

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Objectives: Prostate cancer, after the phase of androgen dependence, may progress to the castration-resistant prostate cancer (CRPC) stage, with resistance to standard therapies. Vitamin E-derived tocotrienols (TTs) possess a significant antitumour activity. Here, we evaluated the anti-cancer properties of δ-TT in CRPC cells (PC3 and DU145) and the related mechanisms of action. Materials and methods:MTT, Trypan blue and colony formation assays were used to assess cell viability/cell death/cytotoxicity. Western blot, immunofluorescence and MTT analyses were utilized to investigate apoptosis, ER stress and autophagy.Morphological changes were investigated by light and transmission electron microscopy. Results:We demonstrated that δ-TT exerts a cytotoxic/proapoptotic activity in CRPC cells. We found that in PC3 cells: (a) δ-TT triggers both the endoplasmic reticulum (ER) stress and autophagy pathways; (b) autophagy induction is related to the ER stress, and this ER stress/autophagy axis is involved in the antitumour activity of δ-TT; in autophagy-defective DU145 cells, only the ER stress pathway is involved in the proapoptotic effects of δ-TT; (c) in both CRPC cell lines, δ-TT also induces an intense vacuolation prevented by the ER stress inhibitor salubrinal and the protein synthesis inhibitor cycloheximide, together with increased levels of phosphorylated JNK and p38, supporting the induction of paraptosis by δ-TT.Conclusions: These data demonstrate that apoptosis, involving ER stress and autophagy (in autophagy positive PC3 cells), and paraptosis are involved in the anti-cancer activity of δ-TT in CRPC cells.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

δ‐Tocotrienol induces apoptosis, involving endoplasmic reticulum stress and autophagy, and paraptosis in prostate cancer cells

et al. 2019

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“…Some recent studies (published in 2011‐2019) are summarized in Table 4. Earlier work has been covered by some excellent recent reviews 7–9,12 and a book 115 . Some of the proposed molecular targets or pathways are highlighted in Figure 3.…”

Section: Laboratory Studies On Ve and Cancer Preventionmentioning

confidence: 99%

“…In 2010, we reviewed the cancer‐preventive activities of tocopherols and tocotrienols 2 . Since then, this topic has been studied by a large number of investigators and reviewed by different authors 7–12 …”

Section: Introductionmentioning

confidence: 99%

Vitamin E and cancer prevention: Studies with different forms of tocopherols and tocotrienols

Yang

Luo

Zeng

et al. 2020

Molecular Carcinogenesis

127

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α‐Tocopherol (α‐T) is the major form of vitamin E (VE) in animals and has the highest activity in carrying out the essential antioxidant functions of VE. Because of the involvement of oxidative stress in carcinogenesis, the cancer prevention activity of α‐T has been studied extensively. Lower VE intake or nutritional status has been shown to be associated with increased cancer risk, and supplementation of α‐T to populations with VE insufficiency has shown beneficial effects in lowering the cancer risk in some intervention studies. However, several large intervention studies with α‐T conducted in North America have not demonstrated a cancer prevention effect. More recent studies have centered on the γ‐ and δ‐forms of tocopherols and tocotrienols (T3). In comparison with α‐T, these forms have much lower systemic bioavailability but have shown stronger cancer‐preventive activities in many studies in animal models and cell lines. γ‐T3 and δ‐T3 generally have even higher activities than γ‐T and δ‐T. In this article, we review recent results from human and laboratory studies on the cancer‐preventive activities of different forms of tocopherols and tocotrienols, at nutritional and pharmacological levels. We aim to elucidate the possible mechanisms of the preventive actions and discuss the possible application of the available information for human cancer prevention by different VE forms.

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“…According to global cancer statistics and GLOBOCAN 2012 (, accessed on 8 July 2018), approximately 14.1 million people are diagnosed with cancer every year and it accounts for 8.2 million deaths worldwide [1]. The significant advancements made in the past few decades for unravelling the molecular causes of cancer have led to the development of numerous treatment modalities including surgery, radiation, and chemotherapy, but the disease burden still remains a challenge [2,3,4,5,6,7]. On the other hand, these chemotherapeutic agents are also associated with adverse side effects like vomiting, hyper tension, cardiovascular diseases, renal dysfunction and bone marrow destruction along with the development of chemoresistance, which further obscures the treatment procedures and ultimately leads to cancer progression and recurrence [8,9,10,11,12,13,14,15,16,17,18].…”

Section: Introductionmentioning

confidence: 99%

Magnolol: A Neolignan from the Magnolia Family for the Prevention and Treatment of Cancer

Ranaware¹,

Banik

Deshpande³

et al. 2018

IJMS

Self Cite

138

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The past few decades have witnessed widespread research to challenge carcinogenesis; however, it remains one of the most important health concerns with the worst prognosis and diagnosis. Increasing lines of evidence clearly show that the rate of cancer incidence will increase in future and will create global havoc, designating it as an epidemic. Conventional chemotherapeutics and treatment with synthetic disciplines are often associated with adverse side effects and development of chemoresistance. Thus, discovering novel economic and patient friendly drugs that are safe and efficacious is warranted. Several natural compounds have proved their potential against this dreadful disease so far. Magnolol is a hydroxylated biphenyl isolated from the root and stem bark of Magnolia tree. Magnolol can efficiently prevent or inhibit the growth of various cancers originating from different organs such as brain, breast, cervical, colon, liver, lung, prostate, skin, etc. Considering these perspectives, the current review primarily focuses on the fascinating role of magnolol against various types of cancers, and the source and chemistry of magnolol and the molecular mechanism underlying the targets of magnolol are discussed. This review proposes magnolol as a suitable candidate that can be appropriately designed and established into a potent anti-cancer drug.

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Tocotrienols: The promising analogues of vitamin E for cancer therapeutics

Cited by 113 publications

References 162 publications

δ‐Tocotrienol induces apoptosis, involving endoplasmic reticulum stress and autophagy, and paraptosis in prostate cancer cells

δ‐Tocotrienol induces apoptosis, involving endoplasmic reticulum stress and autophagy, and paraptosis in prostate cancer cells

Vitamin E and cancer prevention: Studies with different forms of tocopherols and tocotrienols

Magnolol: A Neolignan from the Magnolia Family for the Prevention and Treatment of Cancer

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