Beta-Tocotrienol Exhibits More Cytotoxic Effects than Gamma-Tocotrienol on Breast Cancer Cells by Promoting Apoptosis via a P53-Independent PI3-Kinase Dependent Pathway
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, w...
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2020
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| Online Access: | http://hdl.handle.net/10725/11977 https://doi.org/10.3390/biom10040577 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.mdpi.com/2218-273X/10/4/577/htm |
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| _version_ | 1864513489659232256 |
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| author | Idriss, Maya |
| author2 | Hodroj, Mohammad Hassan Fakhoury, Rajaa Rizk, Sandra |
| author2_role | author author author |
| author_facet | Idriss, Maya Hodroj, Mohammad Hassan Fakhoury, Rajaa Rizk, Sandra |
| author_role | author |
| dc.creator.none.fl_str_mv | Idriss, Maya Hodroj, Mohammad Hassan Fakhoury, Rajaa Rizk, Sandra |
| dc.date.none.fl_str_mv | 2020-07-15T10:01:26Z 2020-07-15T10:01:26Z 2020 2020-07-15 |
| dc.identifier.none.fl_str_mv | 2218-273X http://hdl.handle.net/10725/11977 https://doi.org/10.3390/biom10040577 Idriss, M., Hodroj, M. H., Fakhoury, R., & Rizk, S. (2020). Beta-Tocotrienol Exhibits More Cytotoxic Effects than Gamma-Tocotrienol on Breast Cancer Cells by Promoting Apoptosis via a P53-Independent PI3-Kinase Dependent Pathway. Biomolecules, 10(4), 1-19 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.mdpi.com/2218-273X/10/4/577/htm |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Biomolecules |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | Beta-Tocotrienol Exhibits More Cytotoxic Effects than Gamma-Tocotrienol on Breast Cancer Cells by Promoting Apoptosis via a P53-Independent PI3-Kinase Dependent Pathway |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | 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 α/β 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′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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_5a074c836e5f01c015b5d6b06f0ce78b |
| identifier_str_mv | 2218-273X Idriss, M., Hodroj, M. H., Fakhoury, R., & Rizk, S. (2020). Beta-Tocotrienol Exhibits More Cytotoxic Effects than Gamma-Tocotrienol on Breast Cancer Cells by Promoting Apoptosis via a P53-Independent PI3-Kinase Dependent Pathway. Biomolecules, 10(4), 1-19 |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/11977 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Beta-Tocotrienol Exhibits More Cytotoxic Effects than Gamma-Tocotrienol on Breast Cancer Cells by Promoting Apoptosis via a P53-Independent PI3-Kinase Dependent PathwayIdriss, MayaHodroj, Mohammad HassanFakhoury, RajaaRizk, SandraStudies 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 α/β 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′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.PublishedN/A2020-07-15T10:01:26Z2020-07-15T10:01:26Z20202020-07-15Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article2218-273Xhttp://hdl.handle.net/10725/11977https://doi.org/10.3390/biom10040577Idriss, M., Hodroj, M. H., Fakhoury, R., & Rizk, S. (2020). Beta-Tocotrienol Exhibits More Cytotoxic Effects than Gamma-Tocotrienol on Breast Cancer Cells by Promoting Apoptosis via a P53-Independent PI3-Kinase Dependent Pathway. Biomolecules, 10(4), 1-19http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttps://www.mdpi.com/2218-273X/10/4/577/htmenBiomoleculesinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/119772021-03-19T10:47:40Z |
| spellingShingle | Beta-Tocotrienol Exhibits More Cytotoxic Effects than Gamma-Tocotrienol on Breast Cancer Cells by Promoting Apoptosis via a P53-Independent PI3-Kinase Dependent Pathway Idriss, Maya |
| status_str | publishedVersion |
| title | Beta-Tocotrienol Exhibits More Cytotoxic Effects than Gamma-Tocotrienol on Breast Cancer Cells by Promoting Apoptosis via a P53-Independent PI3-Kinase Dependent Pathway |
| title_full | Beta-Tocotrienol Exhibits More Cytotoxic Effects than Gamma-Tocotrienol on Breast Cancer Cells by Promoting Apoptosis via a P53-Independent PI3-Kinase Dependent Pathway |
| title_fullStr | Beta-Tocotrienol Exhibits More Cytotoxic Effects than Gamma-Tocotrienol on Breast Cancer Cells by Promoting Apoptosis via a P53-Independent PI3-Kinase Dependent Pathway |
| title_full_unstemmed | Beta-Tocotrienol Exhibits More Cytotoxic Effects than Gamma-Tocotrienol on Breast Cancer Cells by Promoting Apoptosis via a P53-Independent PI3-Kinase Dependent Pathway |
| title_short | Beta-Tocotrienol Exhibits More Cytotoxic Effects than Gamma-Tocotrienol on Breast Cancer Cells by Promoting Apoptosis via a P53-Independent PI3-Kinase Dependent Pathway |
| title_sort | Beta-Tocotrienol Exhibits More Cytotoxic Effects than Gamma-Tocotrienol on Breast Cancer Cells by Promoting Apoptosis via a P53-Independent PI3-Kinase Dependent Pathway |
| url | http://hdl.handle.net/10725/11977 https://doi.org/10.3390/biom10040577 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.mdpi.com/2218-273X/10/4/577/htm |