Tocotrienols as an Anti-Breast Cancer Agent

Abstract

In the past few years, breast cancer has become the most prevalent type of cancer. The majority of patients receive combinatorial chemotherapy treatments, which may result in increased risk of developing drug resistance, a reduced quality of life, and substantial side effects. Treatment modalities that could lessen the physical toll of standard treatments or act in synergy with chemotherapeutic treatments would benefit women worldwide. Research into tocotrienols has thus far demonstrated their potential to be such an agent, with tocotrienols surpassing the pharmacological potential of tocopherols. Further research using in vitro and preclinical breast cancer models to support clinical trials is needed. This review uses bibliometric analysis to highlight this gap in research and summarizes the current and future landscape of tocotrienols as an anti-breast cancer agent.

Revisiting the therapeutic potential of tocotrienol

“…199 Among the different types of oxidative damage, DNA oxidation, protein oxidation, and lipid peroxidation are known to produce carcinogenesis, and tocotrienols were identified as having anti-cancer properties that ameliorated the malignant tumors by apoptosis, cell cycle arrest, and disrupted DNA replication and curbed metastasis. 199 DNA oxidation impairs the DNA replication process, and transcription, and upregulates transversion mutations, protein oxidation will lead to peptide chain breakages and susceptibility to proteolysis, while lipid peroxidation results in cell membrane damage in all membrane-bound organelles. 200 Disruption of the plasma membrane would result in the inactivation of signal transduction by denaturing receptors and enzymes.…”

“…Thus, the therapeutic value of vitamin E compounds, particularly the tocotrienols is further enhanced due to its ability to stimulate dual roles by which its anti‐cancer properties are augmented 198 . The prolonged localized cellular inflammatory reactions (generated by dysfunctional electron transport chain in mitochondria, ER and cell membrane, nicotinamide adenine dinucleotide phosphate [NADPH] oxidase, peroxidases, and nitric oxide synthase) can give way to tumorigenesis from which cancers arise, and those cancers have been attenuated by tocotrienols 199 . Among the different types of oxidative damage, DNA oxidation, protein oxidation, and lipid peroxidation are known to produce carcinogenesis, and tocotrienols were identified as having anti‐cancer properties that ameliorated the malignant tumors by apoptosis, cell cycle arrest, and disrupted DNA replication and curbed metastasis 199 .…”

Cancer Prevention Effects of Foods, Food Groups, Nutrients, and Their Underlying Mechanisms

“…Vitamin E is a mixture of eight lipophilic isomers4 saturated tocopherols and 4 unsaturated tocotrienols. , Tocopherols, the major constituent of vitamin E, have been extensively studied on its possible cancer prevention activities (reviewed in ref ). Results from earlier tocopherol studies on cancer prevention were disappointing.…”

“…Another group of natural Vitamin E in particular, tocotrienols, has at least the same anti-oxidant capacity as tocopherols, but is less readily stable . Interestingly, research on tocotrienols has demonstrated their potential as anti-breast cancer agents. ,, Of the tocotrienols, α-tocotrienol has the highest bioavailability, while the γ-tocotrienol and δ-tocotrienol isoforms have more profound anti-cancer properties . For example, the effective anti-tumor activity of γ-tocotrienol induced apoptosis in breast cancer cell lines via upregulation of extrinsic death receptor signaling DR5 .…”

“…Meanwhile, δ-tocotrienol was found to have a high efficacy in inducing apoptosis in human lung adenocarcinoma A549, glioblastoma U87MG, and MDA-MB-231 cells . Based on the discrepancy between tocopherols and tocotrienols, their chemopreventive efficacy on different types of cancers warrants more preclinical and clinical studies.…”