Necroptosis Induced by Delta-Tocotrienol Overcomes Docetaxel Chemoresistance in Prostate Cancer CellsMarina Montagnani Marelli, Giangiacomo Beretta, Roberta Manuela Moretti
International Journal of Molecular Sciences 24 (5), 4923, 2023
Prostate cancer (PCa) represents the fifth cause of cancer death in men. Currently, chemotherapeutic agents for the treatment of cancers, including PCa, mainly inhibit tumor growth by apoptosis induction. However, defects in apoptotic cellular responses frequently lead to drug resistance, which is the main cause of chemotherapy failure. For this reason, trigger non-apoptotic cell death might represent an alternative approach to prevent drug resistance in cancer. Several agents, including natural compounds, have been shown to induce necroptosis in human cancer cells. In this study we evaluated the involvement of necroptosis in anticancer activity of delta-tocotrienol (δ-TT) in PCa cells (DU145 and PC3). Combination therapy is one tool used to overcome therapeutic resistance and drug toxicity. Evaluating the combined effect of δ-TT and docetaxel (DTX), we found that δ-TT potentiates DTX cytotoxicity in DU145 cells. Moreover, δ-TT induces cell death in DU145 cells that have developed DTX resistance (DU-DXR) activating necroptosis. Taken together, obtained data indicate the ability of δ-TT to induce necroptosis in both DU145, PC3 and DU-DXR cell lines. Furthermore, the ability of δ-TT to induce necroptotic cell death may represent a promising therapeutical approach to overcome DTX chemoresistance in PCa.
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Graham49
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The only form of vitamin E I use is from annatto - DeltaGold - mostly for gamma tocotrienol, although the heart-healthy delta tocotrienol is why most use it.
-Patrick
P.S. I forgot to mention that DeltaGold is the best way to supplement with tocotrienols imo. Avoid products that contain DeltaGold, but have some added tocopherols too.
The distinction between tocotrienols and tocopherols (and the use of only dl-alpha tocopheryl acetate) is the reason Vit E was panned in the notoriously flawed SELECT trial.
Tocotrienols: Vitamin E Beyond Tocopherols, Life Sci. 2006 Mar 27; 78(18): 2088–2098.
No tocotrienols were used in SELECT. Even back in 2001 when the trial was started, the distinctions among the various component of Vit E were known. As with the Women's Health Initiative trial on HRT for women, bad design = bad outcomes, leading to poor/confusing advice for patients.
Stay S&W,
Ciao - K9
BTW, You can read the NIH's rationale for the study design (and choices of formulations of both selenium and Vit E used) here:
He obliquely points out the absurdity of giving selenium to those with high levels - including men who are already supplementing.
He could have added that American men already get enough selenium if they eat bread (wheat is grown in selenium-rich soil in the U.S. Europeans are not so lucky. Europe would have been a better setting for SELECT.
The American selenium arm was doomed - too few benefited; too many were poisoned.
The rational for alpha-tocopherol is that it is the dominant isoform in the blood of Americans. Never mind that American diets contain more gama-tocopherol. Perhaps the body has a greater need for the gama form & puts it to use? It is the tocopherol isoform that has by far the greatest effect on PCa - but gamma-tocotrinol is better. Regardless, alpha-tocopherol supplementation drives down both. The law of unintended consequences in action.
Hi Graham. I took six cycles of dosotaxol a few years ago, along with Lupron. It was terribly horrendous. I actually had to stop Lupron during the treatment. It was literally killing me. I have been on it twice for about 2 years altogether out of nine. The chemo and maybe some other patients have received this, but the hair on my chest, under my arms, and on my back left and never came back. I can actually deal with that. NWBO which is being done as APCEDEN in Delhi, Indian definitely saved my life. Back then it was $10,000.00 for six vaccines. It literally took it out of my bone back then and has so far kept it out until now, but I don't feel great, but get up and move around. Took our kids for school supplies last night which was good. Their mom is in Peru. Definitely slowing down. But I am pretty glad to still be here 9 years later so I could watch my kids grow up. The Zytiga had already quit working when I did it and it is still working about 7 years later. I can talk to you more if you want. The vaccines saved my life. Had a radical prostectomy about 4 years ago, but it was hard to remove it. For at least half the time I'd be zero which was great, but had to take Zytiga. If real vaccines like NWBO or APCEDEN are approved maybe even insurance would pay for it. NWBO has done a lot of trials, but none are perfect. With Prostate cancer it was about 30%.
As almost most of the time in such studies, we are not given the amount of the substance required for a clinical effect in humans. The amount may be hundreds if not thousands of mg turning out to be impractical.
If cell research is indicative, LNCaP growth inhibition requires >= 3000 mg of gamma tocotrienols every four hours. This would get your serum level to 19 uM assuming you have a lean weight of 180 lbs.
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