Investigating the Pro-apoptotic, Anti-Cell Proliferation, and Cytotoxic effects of a redox-inactive derivative of Tocotrineol.
TOCOTRIENOLS CAN SUPPORT
INDUCTIONS OF APOPTOSIS
INDUCTION OF CYTOTOXICITY IN MM CELLS
SUPPRESSION OF TUMOR GROWTH
Introduction to Mesothelioma and TocotrienolMalignant Mesothelioma (MM) is a very aggressive cancer and usually occurs in people who have been exposed to asbestos for a long period of time. It is formed in the lining of the abdomen, lungs, and heart. Although restrictions have been placed on asbestos, yet the cases have been increasing owing to its long latency period. The chances of survival are very low for the next five years from the time of prognosis. In this study, a new redox-derivative of Tocotrienol, 6-O-carboxypropyl- α-Tocotrienol to investigate its anti-cancer properties on Mesothelioma cells. The redox derivative of Tocotrienol was introduced to investigate its ability induce strong cytotoxicity on MM cells. Hence, in this study, the focus has been laid on the several anticancer effects like induction of apoptosis, anti-cell proliferation, and cytotoxicity of the redox derivative of Tocotrienol.
How does the Redox Derivative Tocotrienol fight Mesothelioma?In this research, the anti-proliferative effects of Tocotrienol on human malignant mesothelioma cancer cells were discovered. It was observed that Tocotrienols suppress both the activity and expression of HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase which results in suppression of cancer promoting functions like angiogenesis and cell proliferation. MM cells have been observed to have chemo-resistance against cisplatin but when treated with Tocotrienols, the growth of the cancer cells was suppressed! Moreover, the cytotoxic effects of the redox derivative of Tocotrienols on the cancer cells was incredible. It was also observed in the study that the Tocotrienols suppressed the blood supply to the tumor thus preventing the expansion of the tumor mass by inducing anti-angiogenesis and apoptosis in the cancer cells.
Reference for the Study in detail:1. https://www.rarediseasesjournal.com/articles/the-evidence-to-date-a-redoxinactive-analogue-of-tocotrienol-as-a-new-antimesothelioma-agent-raredis-1-1072.php
2. Opitz I. Management of malignant pleural mesothelioma The European experience. J Thorac Dis. 2014; 6(S2): S238-S252.
3. Bonelli MA, Fumarola C, La Monica S, et al. New therapeutic strategies for malignant pleural mesothelioma. Biochem Pharmacol. 2016.
4. Lee AY, Raz DJ, He B, et al. Update on the molecular biology of malignant mesothelioma. Cancer. 2007; 109(8): 1454-1461.
5.Nesaretnam K. Multitargeted therapy of cancer by tocotrienols. Cancer Lett. 2008; 269(2): 388-395.
6. Yano T, Sato A, Sekine M, et al. Redox inactive analogue of tocotrienol as a potential anti cancer agent. Anticancer Agents Med Chem. 2013; 13(3): 496-501.
7. Pearce BC, Parker RA, Deason ME, et al. Hypocholesterolemic activity of synthetic and natural tocotrienols. J Med Chem. 1992; 35(20): 3595-3606.
8. Constantinou C, Papas A, Constantinou AI. Vitamin E and cancer An insight into the anticancer activities of vitamin E isomers and analogs. Int J Cancer. 2008; 123(4): 739-752.
9. Donapaty S, Louis S, Horvath E, et al. RRR α Tocopherol succinate down regulates oncogenic Ras signaling. Mol Cancer Ther. 2006; 5(2): 309-16.
10.Tomasetti M, Gellert N, Procopio A, et al. A vitamin E analogue suppresses malignant mesothelioma in a preclinical model a future drug against a fatal neoplastic disease. Int J Cancer. 2004; 109(5): 641-642.
11. Neuzil J. Alpha tocopheryl succinate epitomizes a compound with a shift in biological activity due to pro vitamin to vitamin conversion. Biochem Biophys Res Commun. 2002; 293(5): 1309-1313.
12. Fariss MW, Fortuna MB, Everett CK, et al. The selective antiproliferative effects of alpha tocopheryl hemisuccinate and cholesteryl hemisuccinate on murine leukemia cells result from the action of the intact compounds. Cancer Res. 1994; 54(13): 3346-3351.
13. Pierpaoli E, Viola V, Pilolli F, et al. Gamma and delta tocotrienols exert a more potent anticancer effect than alpha tocopheryl succinate on breast cancer cell lines irrespective of HER-2/neu expression. Life Sci. 2010; 86(17-18): 668-675.
14.Birringer M, Pfluger P, Kluth D, et al. Identities and differences in the metabolism of tocotrienols and tocopherols in HepG2 cells. J Nutr. 2002; 132(10): 3113-3118.
15. Suzuki YJ, Tsuchiya M, Wassall SR, et al. Structural and dynamic membrane properties of alpha-tocopherol and alpha tocotrienol implication to the molecular mechanism of the antioxidant potency. Biochemistry. 1993; 32(40): 10692-10699.
16. Yano Y, Satoh H, Fukumoto K, et al. Induction of cytotoxicity in human lung adenocarcinoma cells by 6 O carboxypropyl alpha tocotrienol a redox silent derivative of alpha tocotrienol. Int J Cancer. 2005; 115(5): 839-846.
17. Kozin SV, Shkarin P, Gerweck LE. The cell transmembrane pH gradient in tumors enhances cytotoxicity of specific weak acid chemotherapeutics. Cancer Res. 2001; 61(12): 4740-4743.