27/10/2004 (NewsRx.com & NewsRx.net) -- By studying cancer in mice,researchers at the University of Texas at Austin have gained preliminaryevidence that a novel compound that resembles vitamin E halves the size oftumors and the ability of cancer to spread to other body sites.
"We have clear evidence that this chemical is directly causing cancercells to die," said Kimberly Kline, a nutrition professor in thedepartment of human ecology who directed the research in collaborationwith Bob G. Sanders, a professor in the School of Biological Sciences.
The findings are published in the October 2004 issue of ExperimentalBiology and Medicine. They result from studies involving treatment ofgenetically identical mice, which were given the novel vitamin E compoundeither orally or by aerosol.
Based on earlier, similar findings by Kline and colleagues, the U.S.National Cancer Institute is funding national efforts to investigate theability of this novel compound, RRR-alpha-tocopherol ether acetic analog(alpha-TEA), to prevent colon and breast cancers in preclinical animalmodels.
Mice in the study were treated with alpha-TEA for 21 days after aninjection of mouse-derived mammary cancer cells that normally would haveformed a tumor mass and spread to the animals' lungs. Regardless ofwhether alpha-TEA was administered to the mice by mouth (orally) or viabreathing (aerosol), the compound was capable of reducing the primarytumor mass by greater than half.
In addition, the compound was capable of reducing tumor lesions(metastases) in the lung that were big enough to see with the naked eye.For example, only 1 of 10 alpha-TEA aerosol-treated mice developed visiblelung tumor lesions in comparison to 5 of 10 untreated control mice. Noneof the treated animals showed any type of general symptoms of toxicity toalpha-TEA, which Kline chose for further study in 1997 from 50 candidates.
Because cancer may result from just one normal cell going awry, Kline andformer graduate student Karla Lawson also used special microscopeequipment to identify smaller cancer lesions. The equipment could pinpointthe injected cancer cells in the animals because the cells had previouslybeen genetically modified by coauthor LuZhe Sun from the University ofTexas Health Science Center in San Antonio to fluoresce bright green underproper exposure.
Using this fluorescent cue, Kline and colleagues determined that micetreated with aerosolized alpha-TEA had less than half the number of lungmicrometastases as untreated mice (an average of 31 vs. 73 detected cancercells or small clusters of such cells). In addition, 48% of nearby lymphnodes of those mice lacked any microscopic signs of cancer, though thesestructures are where the cancer would likely spread. Only 4% oflung-related lymph nodes in controls were cancer-free. Treated mice thatdid develop microscopic signs of cancer in the lymph nodes had only one ortwo lesions, rather than the six or seven of untreated counterparts.
Kline, who holds the Julian C. Barton Professorship in Nutrition, alsoinvestigated how alpha-TEA impacts breast cancer cells, using cells grownin plastic containers. When exposed to alpha-TEA, the cancer cells showedonly 20% of their normal ability to multiply and produce new cells. Inaddition to blocking the cancer cells' ability to divide, alpha-TEA causedthe cancer cells to shrink and die through a process called apoptosiscompared to untreated breast cancer cells.
"One reason that alpha-TEA is such a potent anticancer agent is that itimpacts on numerous antigrowth and pro-death cellular processes in cancercells but not normal cells," said Kline.
The researchers also investigated whether another derivative of vitamin Ecalled RRR-alpha-tocopheryl succinate or VES, was as effective. VES waseffective when administered by aerosol but was not effective when givenorally, probably because it is broken down into an inactive chemical formby intestinal enzymes.
Kline will continue analyzing alpha-TEA activity and cellular effects inmice. Meanwhile, the chemical is going through more detailed toxicityevaluations and analyses for its preventive and treatment potential byresearchers receiving support from the Rapid Access to PreventiveIntervention Development (RAPID) program of the National Cancer Institute.
"Our research is promising at this stage, but there's a lot of furtherinvestigations that have to be conducted before alpha-TEA can be cleared... for testing in humans," Kline said.
This article was prepared by Women's Health Weekly editors from staff andother reports.