Gamma-tocotrienol acts as a BH3 mimetic to induce apoptosis in neuroblastoma SH-SY5Y cells
Bcl-2 family proteins are crucial regulators of apoptosis. Both pro- and antiapoptotic members exist, and overexpression of the latter facilitates evasion of apoptosis in many cancer types. Bcl-2 homology domain 3 (BH3) mimetics are small molecule inhibitors of antiapoptotic Bcl-2 family members, an...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016
|
| Online Access: | http://psasir.upm.edu.my/id/eprint/35197/ http://psasir.upm.edu.my/id/eprint/35197/1/Gamma-tocotrienol%20acts%20as%20a%20BH3%20mimetic%20to%20induce%20apoptosis%20in%20neuroblastoma%20SH-SY5Y%20cells.pdf |
| _version_ | 1848847987439042560 |
|---|---|
| author | Tan, Jen Kit Then, Sue Mian Mazlan, Musalmah Raja Abdul Rahman, Raja Noor Zaliha Jamal, Rahman Wan Ngah, Wan Zurinah |
| author_facet | Tan, Jen Kit Then, Sue Mian Mazlan, Musalmah Raja Abdul Rahman, Raja Noor Zaliha Jamal, Rahman Wan Ngah, Wan Zurinah |
| author_sort | Tan, Jen Kit |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Bcl-2 family proteins are crucial regulators of apoptosis. Both pro- and antiapoptotic members exist, and overexpression of the latter facilitates evasion of apoptosis in many cancer types. Bcl-2 homology domain 3 (BH3) mimetics are small molecule inhibitors of antiapoptotic Bcl-2 family members, and these inhibitors are promising anticancer agents. In this study, we report that gamma-tocotrienol (γT3), an isomer of vitamin E, can inhibit Bcl-2 to induce apoptosis. We demonstrate that γT3 induces cell death in human neuroblastoma SH-SY5Y cells by depolarising the mitochondrial membrane potential, enabling release of cytochrome c to the cytosol and increasing the activities of caspases-9 and -3. Treatment of cells with inhibitors of Bax or caspase-9 attenuated the cell death induced by γT3. Simulated docking analysis suggested that γT3 binds at the hydrophobic groove of Bcl-2, while a binding assay showed that γT3 competed with a fluorescent probe to bind at the hydrophobic groove. Our data suggest that γT3 mimics the action of BH3-only protein by binding to the hydrophobic groove of Bcl-2 and inducing apoptosis via the intrinsic pathway in a Bax- and caspase-9-dependent manner. |
| first_indexed | 2025-11-15T09:27:20Z |
| format | Article |
| id | upm-35197 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T09:27:20Z |
| publishDate | 2016 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-351972016-10-11T02:54:45Z http://psasir.upm.edu.my/id/eprint/35197/ Gamma-tocotrienol acts as a BH3 mimetic to induce apoptosis in neuroblastoma SH-SY5Y cells Tan, Jen Kit Then, Sue Mian Mazlan, Musalmah Raja Abdul Rahman, Raja Noor Zaliha Jamal, Rahman Wan Ngah, Wan Zurinah Bcl-2 family proteins are crucial regulators of apoptosis. Both pro- and antiapoptotic members exist, and overexpression of the latter facilitates evasion of apoptosis in many cancer types. Bcl-2 homology domain 3 (BH3) mimetics are small molecule inhibitors of antiapoptotic Bcl-2 family members, and these inhibitors are promising anticancer agents. In this study, we report that gamma-tocotrienol (γT3), an isomer of vitamin E, can inhibit Bcl-2 to induce apoptosis. We demonstrate that γT3 induces cell death in human neuroblastoma SH-SY5Y cells by depolarising the mitochondrial membrane potential, enabling release of cytochrome c to the cytosol and increasing the activities of caspases-9 and -3. Treatment of cells with inhibitors of Bax or caspase-9 attenuated the cell death induced by γT3. Simulated docking analysis suggested that γT3 binds at the hydrophobic groove of Bcl-2, while a binding assay showed that γT3 competed with a fluorescent probe to bind at the hydrophobic groove. Our data suggest that γT3 mimics the action of BH3-only protein by binding to the hydrophobic groove of Bcl-2 and inducing apoptosis via the intrinsic pathway in a Bax- and caspase-9-dependent manner. Elsevier 2016 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/35197/1/Gamma-tocotrienol%20acts%20as%20a%20BH3%20mimetic%20to%20induce%20apoptosis%20in%20neuroblastoma%20SH-SY5Y%20cells.pdf Tan, Jen Kit and Then, Sue Mian and Mazlan, Musalmah and Raja Abdul Rahman, Raja Noor Zaliha and Jamal, Rahman and Wan Ngah, Wan Zurinah (2016) Gamma-tocotrienol acts as a BH3 mimetic to induce apoptosis in neuroblastoma SH-SY5Y cells. The Journal of Nutritional Biochemistry, 31. pp. 28-37. ISSN 0955-2863; ESSN: 1873-4847 http://www.sciencedirect.com/science/article/pii/S0955286316000292 10.1016/j.jnutbio.2015.12.019 |
| spellingShingle | Tan, Jen Kit Then, Sue Mian Mazlan, Musalmah Raja Abdul Rahman, Raja Noor Zaliha Jamal, Rahman Wan Ngah, Wan Zurinah Gamma-tocotrienol acts as a BH3 mimetic to induce apoptosis in neuroblastoma SH-SY5Y cells |
| title | Gamma-tocotrienol acts as a BH3 mimetic to induce apoptosis in neuroblastoma SH-SY5Y cells |
| title_full | Gamma-tocotrienol acts as a BH3 mimetic to induce apoptosis in neuroblastoma SH-SY5Y cells |
| title_fullStr | Gamma-tocotrienol acts as a BH3 mimetic to induce apoptosis in neuroblastoma SH-SY5Y cells |
| title_full_unstemmed | Gamma-tocotrienol acts as a BH3 mimetic to induce apoptosis in neuroblastoma SH-SY5Y cells |
| title_short | Gamma-tocotrienol acts as a BH3 mimetic to induce apoptosis in neuroblastoma SH-SY5Y cells |
| title_sort | gamma-tocotrienol acts as a bh3 mimetic to induce apoptosis in neuroblastoma sh-sy5y cells |
| url | http://psasir.upm.edu.my/id/eprint/35197/ http://psasir.upm.edu.my/id/eprint/35197/ http://psasir.upm.edu.my/id/eprint/35197/ http://psasir.upm.edu.my/id/eprint/35197/1/Gamma-tocotrienol%20acts%20as%20a%20BH3%20mimetic%20to%20induce%20apoptosis%20in%20neuroblastoma%20SH-SY5Y%20cells.pdf |