Combined Gamma-Tocotrienol and Statin Treatment for Malignant Mesothelioma

by | Apr 26, 2016 | 2013, Lung Health, Mesothelioma, Tocotrienols

Written by Joyce Smith, BS. This cell study shows how gamma-tocotrienol and statins, when used in combination, were more effective in destroying malignant melanoma cell lines than when used alone.

Malignant mesothelioma is a rare and aggressive treatment- resistance cancer. At least 80 % of all malignant mesotheliomas are the result of exposure to asbestos at some point in one’s lifetime [1, 2]. Over a 15-year time span (between 1994-2008) this type of cancer increased in numbers by 174,300 [3]. Asbestos is a key player in the pathogenesis of malignant mesothelioma and contributes greatly to its rapid proliferation and development of resistance to drug therapies. It is for this reason that new treatment modalities are urgently needed for this difficult to treat disease. [4]

Gamma tocotrientol, a form of vitamin E, causes cell death in a variety of cancer cell types. [5] It has stronger anticancer, neuroprotective and cholesterol lowering activities than other forms of vitamin E [6, 7]. Just recently gamma tocotrienol [y-T3] has demonstrated anticancer activities in human cancers including cancers of the prostate [8], breast [9], colon [10] and liver [11]. Statins, which are widely used and known for their ability to inhibit cholesterol production [12], are also capable of blocking tumor growth in vivo and in vitro and inducing cell death [13]. While they demonstrate strong anti cancer effects, they are also very toxic at the high doses required to treat cancers, thus treatment with statins has been limited to lifestyle diseases.

This study postulates that a combination of gamma tocotrienol [y-T3] and the statins atorvastatin [ATV] and simvastatin [SMV] might work together synergistically to provide a more effective chemotherapeutic drug with less toxicity than a high dose statin used alone. To that end researchers treated four different human MM cell lines: epithelioid [H28], sarcomatoid [H2052)], and two diphasic [H2452 and MSTO] with y-T3 alone and in combination with ATV and SMV. After 24 and 48 hours of treatment they examined the toxic effects on all 4 MM cell lines and found that y-T3 in combination with statins significantly inhibited the growth of human MM cells in a time dependent manner compared to y-T3 or statin alone. [p=<0.01; p=<0.001]

To find out how this combination of yT3 and statins worked researchers chose the diphasic sarcomatoid (MSTO) and epithelioid (H2452) MM cell lines for the follow-up study because they proved more sensitive to the y-T3 and statin combination than the epithelioid and sarcomatoid cell lines.

Researchers treated y-T3 and statins ATV and SMV alone and in combination on MSTO and H2452 cells to determine the mechanisms by which cell death occurred. They found that the y-T3 and statin combination inhibited cell growth more than each single treatment. They also found that cell death occurred when y-T3 activated endoplasmic reticulum stress markers that initiated pathways leading to cancer cell death.

These results suggest that a synergistic combination of y-T3 and statins may significantly inhibit cancer cell growth and “help to overcome the resistance of human malignant mesothelioma to current therapies,” thus making it a useful treatment option for malignant mesothelioma.

Source: Tuerdi, Guligena, et al. “Synergistic effect of combined treatment with gamma-tocotrienol and statin on human malignant mesothelioma cells.” Cancer letters 339.1 (2013): 116-127.

© 2013 Elsevier Ireland Ltd. All rights reserved

Posted June 29, 2015.

*Prescription drugs can save lives but may also cause unwanted side effects. Thus not all drugs are considered safe. Consult with your medical healthcare provider for more information on a specific drug of interest.

Cell culture studies are done on cells maintained artificially in a laboratory environment outside the body. These studies can be completed relatively quickly and are generally used to evaluate the mechanism of action, dose response, or the potential toxicity levels of a substance. Cell studies can identify the feasibility of additional clinical research in animal and human studies to confirm the results predicted by cell culture studies.

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