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Life Extension Magazine

LE Magazine September 1999

Q & A


Vitamin E Succinate
A Question of Treatment and Prevention

Q and A Q In you new breast cancer protocol, you discuss the advantages of vitamin E succinate in particular. However, in the abstracts, the only mention I could find of any vitamin E was in "Apparent partial remission of breast cancer in 'high risk' patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10," Mol Aspects Med (England) 1994, 15 Suppl. This reference did not mention succinate specifically. Is there another abstract that supports the protocol?

A To follow are a few abstracts showing the effectiveness of vitamin E succinate for breast cancer treatment and prevention:

Vitamin E succinate (VES) induces Fas sensitivity in human breast cancer cells: role for Mr 43,000 Fas in VES-triggered apoptosis
Fas (CD95/APO-1) is an important mediator of apoptosis. We show that Fas-resistant MCF-7, MDA-MB-231, and MDA-MB-435 human breast cancer cells become responsive to anti-Fas (CD95) agonistic antibody-triggered apoptosis after pretreatment or cotreatment with vitamin E succinate (VES; RRR-alpha-tocopheryl succinate). In contrast, no enhancement of anti-Fas agonistic antibody-triggered apoptosis was observed following VES pretreatment or cotreatment with Fas-sensitive primary cultures of human mammary epithelial cells, immortalized MCF-10A cells, or T47D human breast cancer cells. Although VES is itself a potent apoptotic triggering agent, the 6-h pretreatment procedure for Fas sensitization did not initiate VES-mediated apoptosis. The combination of VES plus anti-Fas in pretreatment protocols was synergistic, inducing 2.8-, 3.0-, and 6.3-fold enhanced apoptosis in Fas-resistant MCF-7, MDA-MB-231, and MDA-MB-435 cells, respectively. Likewise, cotreatment of Fas-resistant MCF-7, MDA-MB-231, and MDA-MB-435 cells with VES plus anti-Fas enhanced apoptosis 1.9-, 2.0-, and 2.6-fold, respectively. Functional knockout of Fas-mediated signaling with either Fas-neutralizing antibody (MCF-7-, MDA-MB-231-, and MDA-MB-435-treated cells) or Fas antisense oligomers (MDA-MB-435-treated cells only), reduced VES-triggered apoptosis by approximately 50%. Analyses of whole cell extracts from Fas-sensitive cells revealed high constitutive expression of Mr 43,000 Fas, whereas Fas-resistant cells expressed low levels that were confined to the cytosolic fraction. VES treatment of the Fas-resistant cells caused a depletion of cytosolic Mr 43,000 Fas with a concomitant increase in Mr 43,000 membrane Fas. These data show that VES can convert Fas-resistant human breast cancer cells to a Fas-sensitive phenotype, perhaps by translocation of cytosolic Mr 43,000 Fas to the membrane and show that VES-mediated apoptosis involves Mr 43,000 Fas signaling.

Cancer Res 1999 Feb 15;59(4):953-61

Vitamin E succinate inhibits proliferation of BT-20 human breast cancer cells: increased binding of cyclin A negatively regulates E2F transactivation activity
Vitamin E succinate (VES) inhibited the proliferation of the estrogen receptor-negative human breast cancer cell line, BT-20, in the G1 phase of the cell cycle. The E2F proteins are integral transcriptional components in the regulation of cell growth. Overexpression of E2F-1 blocked the ability of VES to inhibit BT-20 cell growth, suggesting that VES regulation of E2F-1 activity leads to growth arrest of BT-20 cells. VES, although having little effect on E2F-1 steady-state protein levels, decreased E2F-1 phosphorylation and transactivation activity and increased cyclin A binding to E2F-1. GAL4-E2F-1 deletion mutant studies indicated that cyclin A negatively regulates E2F function. In VES-treated BT-20 cells, the cyclin A protein exhibited reduced kinase activity, which correlated with decreased steady-state levels and binding of cyclin-dependent kinase-2 to cyclin A and increased steady-state levels and binding of p21cip1 to cyclin A and cyclin-dependent kinase-2. The functional consequence of the negative regulatory effect of VES on E2F-1 function was shown by the ability of VES to inhibit the transcriptional activation of an E2F-1 responsive gene, c-myc. These studies show that VES induces growth inhibition of BT-20 cells through a mechanism that involves cyclin A-negative regulation of E2F-mediated transcription.

Cancer Res 1997 Jul 1;57(13):2668-75

Vitamin E succinate induces Fas-mediated apoptosis in estrogen receptor-negative human breast cancer cells
Vitamin E succinate (VES), a derivative of the fat-soluble vitamin D-alpha-tocopherol (vitamin E), inhibited growth and induced apoptotic cell death of estrogen receptor-negative human breast cancer cells. VES-induced apoptosis in MDA-MB-231 and SKBR-3 cells occurred through a Fas pathway. Total protein levels of the Fas receptor (Fas; APO-1/CD-95) and the Fas ligand (Fas-L) were increased following VES treatment. In addition, VES increased cell surface Fas expression. Fas-neutralizing antibodies and Fas-L antisense oligonucleotides blocked VES-induced apoptosis. The presence of Fas-L antisense oligonucleotides also completely blocked the VES-mediated increase in Fas-L protein expression. These data indicate a role for Fas signaling in VES-mediated apoptotic cell death of human breast cancer cells. These findings also suggest that VES may be of clinical use in the treatment of aggressive human breast cancers, particularly those that are refractory to antiestrogen therapy.

Cancer Res 1997 Mar 1;57(5):881-90


Q I have been taking SAMe and it's great, but it is also expensive to keep up on. Can trimethylglycine (TMG) be used as a substitute for SAMe as an antidepressant?

A For purposes of depression, it is usually not possible to take enough TMG as a substitute for SAMe. The reason is that only a portion of the TMG will be broken down into SAMe.


Q Does Vinpocetine have the potential to produce the same dangerous side effects as Viagra? After all, isn't Vinpocetine's mode of action similar to that of Viagra? In reading Life Extension's articles on Vinpocetine I have alleviated some of my concerns of side effects. However, Viagra's side effects did not show up until millions began to take it. Could you please comment?

A Vinpocetine does not have the same pharmacological actions as Viagra. The only reported and known side effect of Vinpocetine is a headache. Only a small percentage of individuals will experience this side effect, which is not to be compared with any of the side effects caused by Viagra.


Q I was impressed to read about how taking chitosan capsules (3 capsules, a half hour before a meal) can help to effectively eliminate excess fat from the body. However, I drink Chinese tea through out the whole day, and wonder whether doing so could interrupt with the performance of chitosan. What do you think?

A Chinese tea will not interfere with the effectiveness of chitosan. It is only fat solubles and essential fatty acids that may do so. Therefore, we recommend that you take chitosan separately from fat soluble nutrients, such as vitamin E, essential fatty acids, CoQ10 in oil base, Gamma E or uncooked oils used in meals. Allow a couple of hours, at least, between taking these items and chitosan.


Q I read the articles on green tea you published in the June 1999 issue of Life Extension magazine with great interest, and was particularly intrigued by green tea's effects on cancer. Do you have any specific information regarding green tea's effects on leukemia?

A Here is an abstract regarding green tea's effects on leukemia.

Growth inhibition of leukemic cells by (-)-epigallocatechin gallate, the main constituent of green tea
In this report, we presented the results that EGCG, the main constituent of the polyphenols present in Japanese green tea inhibited growth of leukemic cell lines of both human and mice. The proliferation of human leukemic cell lines and mouse NFS60 cell line was inhibited by EGCG. Sensitivity of each line to EGCG was different, and more than 50% of DNA synthesis was reduced in all the cell lines in the presence of 50 microM EGCG. On the other hand, normal hematopoietic progenitor cells retained their natural function of supplying mature cells of various lineages in the presence of less than 10 microM EGCG in vitro. Even in the presence of 100 microM EGCG, half the colonies containing all the lineages of cells were developed. All the dead cells of each line showed characteristics of apoptosis, which might be due to inhibition by EGCG of growth factors' signaling. Besides anticarcinogenic activity, EGCG is expected to have a new function for leukemia therapy without side effects.

Life Sci, 63(16):1397-403 1998