Beta-Tocotrienol Exhibits More Cytotoxic Effects than Gamma-Tocotrienol on Breast Cancer Cells by Promoting Apoptosis via a P53-Independent PI3-Kinase Dependent Pathway

Autor:	Mohammad Hassan Hodroj, Maya Idriss, Rajaa Fakhoury, Sandra Rizk
Rok vydání:	2020
Předmět:	0301 basic medicine medicine.medical_treatment lcsh:QR1-502 Breast Neoplasms vitamin E Biochemistry lcsh:Microbiology Article 03 medical and health sciences chemistry.chemical_compound Inhibitory Concentration 50 Phosphatidylinositol 3-Kinases 0302 clinical medicine breast cancer Downregulation and upregulation Cell Line Tumor medicine beta-tocotrienol Humans Viability assay beta-Tocotrienol Chromans Molecular Biology gamma-Tocotrienol Cell Proliferation Cell Death Kinase Vitamin E Cell Cycle apoptosis Cell Cycle Checkpoints Up-Regulation 030104 developmental biology chemistry Cell culture Apoptosis 030220 oncology & carcinogenesis Cancer research gamma-tocotrienol Female Tumor Suppressor Protein p53
Zdroj:	Biomolecules Biomolecules, Vol 10, Iss 577, p 577 (2020) Volume 10 Issue 4
ISSN:	2218-273X
Popis:	Studies on tocotrienols have progressively revealed the benefits of these vitamin E isoforms on human health. Beta-tocotrienol (beta-T3) is known to be less available in nature compared to other vitamin E members, which may explain the restricted number of studies on beta-T3. In the present study, we aim to investigate the anti-proliferative effects and the pro-apoptotic mechanisms of beta-T3 on two human breast adenocarcinoma cell lines MDA-MB-231 and MCF7. To assess cell viability, both cell lines were incubated for 24 and 48 h, with different concentrations of beta-T3 and gamma-T3, the latter being a widely studied vitamin E isoform with potent anti-cancerous properties. Cell cycle progression and apoptosis induction upon treatment with various concentrations of the beta-T3 isoform were assessed. The effect of beta-T3 on the expression level of several apoptosis-related proteins p53, cytochrome C, cleaved-PARP-1, Bax, Bcl-2, and caspase-3, in addition to key cell survival proteins p-PI3K and p-GSK-3 &alpha /&beta was determined using western blot analysis. Beta-tocotrienol exhibited a significantly more potent anti-proliferative effect than gamma-tocotrienol on both cell lines regardless of their hormonal receptor status. Beta-T3 induced a mild G1 arrest on both cell lines, and triggered a mitochondrial stress-mediated apoptotic response in MDA-MB-231 cells. Mechanistically, beta-T3&prime s anti-neoplastic activity involved the downregulation of phosphorylated PI3K and GSK-3 cell survival proteins. These findings suggest that vitamin E beta-T3 should be considered as a promising anti-cancer agent, more effective than gamma-T3 for treating human breast cancer and deserves to be further studied to investigate its effects in vitro and on other cancer types.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::16124daae7310863321c58048956c185 https://pubmed.ncbi.nlm.nih.gov/32283796 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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