Positive Health Online

Abstract

PUSSINEN and colleagues, Institute of Medical Biochemistry, Graz, Austria investigated whether alpha-tocopheryl succinate(alpha-TS) -enriched lipoproteins inhibited breast cancer cell growth in a manner comparable to the free drug.

Background

Alpha-tocopheryl succinate (alpha-TS) is a potent inhibitor of tumour cell proliferation .

Methodology

To study the association of alpha-TS with lipoproteins, human plasma was enriched with alpha-TS in vitro. To study whether the level of LDL-receptor (LDL-R) expression affects alpha-TS uptake from apoB/E-containing lipoprotein particles, human breast cancer cells with low (MCF-7) and normal (HBL-100) (LDL-R) expression were used. To investigate effects on apoptosis (programmed cell death), these cell lines were incubated in the presence of free or lipoprotein-associated alpha-TS and analysed for DNA fragmentation.

Results

Alpha-TS readily associated with the main lipoprotein classes in vitro, and these findings were confirmed in vivo in mice. The highest alpha-TS concentrations generated lipoproteins carrying 50,000 (VLDL), 5,000 (LDL) and 700 (HDL) alpha-TS molecules per lipoprotein particle. Alpha-TS-enriched lipoproteins had lipoprotein particles of slightly decreased density and increased radius . The uptake of free, VLDL- and (apoE-free) HDL(3)-associated alpha-TS was nearly identical in human breast cancer cells with low (MCF-7) versus normal (HBL-100) (LDL-R) expression. In contrast, uptake of LDL-associated alpha-TS by HBL-100 cells (normal LDL-R expression ) was about twice as high as that by MCF-7 cells (low LDL-R expression ). VLDL- and LDL-associated alpha-TS inhibition cell proliferation most effectively (100% inhibition of MCF-7 growth) at the highest concentration of alpha-TS used (20 ug/ml lipoprotein-associated alpha-TS). However, alpha-TS-free VLDL and LDL also inhibited HBL-100 cell proliferation by up to 55%. Alpha-TS-enriched HDL inhibited growth of both cells lines by 40-60%. Incubation of either cell line with free or lipoprotein-associated alpha-TS resulted in DNA fragmentation indicative of apoptosis .

Conclusion

Alpha-TS readily associated with lipoproteins in vitro and in vivo. Efficacy of lipoprotein enrichment depended on lipoprotein particle size and/or triglyceride content . Uptake of LDL-associated alpha-TS appeared to depend on the level of LDL-R expression . Lipoproteins were efficient carriers of alpha-TS – alpha-TS-enriched lipoproteins reduced cell proliferation rates and induced apoptosis in human breast cancer cells in a manner similar to the free drug .

References

Pussinen PJ et al. Lipoprotein-associated alpha-tocopheryl-succinate inhibits cell growth and induces apoptosis in human MCF-7 and HBL-100 breast cancer cells. Biochimica et Biophysica Acta 1485 (2-1): 129-44. May 2000.

Comment

When I was first compiling the document which became the Consensus Document Nutrition and Lifestyle Guidelines for People with Cancer (J Nutr Med 4: 199-214. 1994), there was a question raised by the Bristol Cancer Help Centre regarding whether vitamin E was somehow deleterious in the treatment of breast cancer. At the time, none of the professionals present knew of any evidence; during the intervening years the opposite evidence has emerged that vitamin E shows great promise in the treatment of breast cancer as the above research readily demonstrates.