TOCOTRIENOLS CAN SUPPORT
CANCER CELL CYCLE ARREST
APOPTOSIS IN LEUKAEMIA CANCER CELLS
CYTOTOXICITY IN LEUKAEMIA CANCER CELL LINES
Introduction to Leukaemia and Gamma-TocotrienolLeukemia is a type of blood cancer that is caused when white blood cells in the body start multiplying abnormally in large numbers and start harming the red blood cells and the platelets.
Gamma-Tocotrienols along with statins modulate the cholesterol biosynthesis pathway by inhibiting HMG-CoA reductase by post-transcriptional downregulation. This mechanism leads to cancer cell cycle arrest, apoptosis, and suppression of cancer cell proliferation. Several studies have also shown that statins suppress certain actions of acute myelocytic leukemia cells. Since both gamma-Tocotrienols and Statins, both, are associated with the decrease in cholesterol biosynthesis, hence it was investigated if the combination of these drugs could synergize in cytotoxicity on leukemic cells.
How does Gamma-Tocotrienol fight Leukaemia or Blood Cancer?In the study, it was observed that both Gamma-Tocotrienol and Simvastatin induced cytotoxicity in K-562 and HL-60 cell lines by the MTS and Cell Titer Glo Assays. In the study, it was shown that Simvastatin which is a cholesterol-lowering drug, and Gamma-Tocotrienol which is an antioxidant, were together able to exhibit synergy in the induction of cytotoxicity in K-562 and HL-60 leukemia cancer cell lines. All the mechanisms combined resulted in cell cycle arrest, inductions of apoptosis, and suppression of cancer cell proliferation.
Reference for the Study in detail:1.https://ashpublications.org/blood/article/122/21/4927/14222/Gamma-Tocotrienol-and-Simvastatin-Synergistically
4.R.S. Wong, A.K. Radhakrishnan, T.A. Ibrahim, S.K. Cheong, δ- and γ-tocotrienols induce classical ultrastructural apoptotic changes in human T lymphoblastic leukemic cells, Microsc Microanal. 18 (2012) 462-469.
5.R.S. Wong, A.K. Radhakrishnan, T.A. Ibrahim, S.K. Cheong, δ- and γ-tocotrienols induce classical ultrastructural apoptotic changes in human T lymphoblastic leukemic cells, Microsc Microanal. 18 (2012) 462-469.
6.C.C. Chen, T.Y. Liu, S.P. Huang, C.T. Ho, T.C. Huang, Differentiation and apoptosis induction by lovastatin and γ-tocotrienol in HL-60 cells via Ras/ERK/NF-κB and Ras/Akt/NF-κB signaling dependent down-regulation of glyoxalase 1 and HMG-CoA reductase. Cell Signal. 27 (2015) 2182-2190.
7.A. Inoue, K. Takitani, M. Koh, C. Kawakami, T. Kuno, H. Tamai, Induction of apoptosis by γ-tocotrienol in human cancer cell lines and leukemic blasts from patients: dependency on Bid, cytochrome c, and caspase pathway, Nutr Cancer. 63 (2011) 763-770
8.M.L. de Mesquita, R.M. Araújo, D.P. Bezerra, R.B. Filho, J.E. de Paula, E.R. Silveira, C. Pessoa, M.O. de Moraes, L.V. Costa Lotufo, L.S. Espindola, Cytotoxicity of δ-tocotrienols from Kielmeyera coriacea against cancer cell lines, Bioorg Med Chem. 19 (2011) 623-630.