Vitamin E analog alpha-TEA and celecoxib alone and together reduce human MDA-MB-435-FL-GFP breast cancer burden and metastasis in nude mice.
Alpha-TEA, a nonhydrolyzable ether analog of vitamin E (RRR-alpha-tocopherol), and celecoxib, a specific COX-2 inhibitor, were delivered separately or in combination to investigate their anticancer properties, using MDA-MB-435-FL-GFP human breast cancer xenografts in nude mice. Liposomal formulated alpha-TEA administered as an aerosol and celecoxib fed at 500 or 1250 mg/kg diet for 31 days separately or in combination significantly reduced tumor volume in comparison to control (p < 0.001 for all treatment groups). Of special note, the combinations of alpha-TEA + celecoxib (1250) inhibited tumor volume significantly better than either single treatment (p < 0.001 and p < 0.001). Average number of macroscopic lung metastases were significantly reduced in all treatment groups in comparison to control, with the exception of celecoxib (500). Mean numbers of microscopic lung and lymph node metastases in all treatment groups were significantly lower than control. Furthermore, the mean number of microscopic lung metastases in the alpha-TEA+celecoxib (1250) group were significantly lower than either separate treatment. Analyses of 5 microm tumor sections showed that all treatments, with the exception of celecoxib (500) alone, significantly enhanced apoptosis (TUNEL) and significantly decreased cell proliferation (Ki-67). alpha-TEA and alpha-TEA + celecoxib (1250) treatments significantly reduced blood vessel density (CD-31) in comparison to control. These data show promise for combination alpha-TEA + celecoxib chemotherapy for breast cancer.
Zhang
Shuo
S
Division of Nutrition/A2703, University of Texas at Austin, Austin, TX 78712-1097, USA.
Lawson
Karla A
KA
Simmons-Menchaca
Marla
M
Sun
LuZhe
L
Sanders
Bob G
BG
Kline
Kimberly
K
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000662:veterinary; D000068579:Celecoxib; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008081:Liposomes; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary* / Q000662:veterinary; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D011720:Pyrazoles; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D024505:Tocopherols; D014183:Transplantation, Heterologous; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*
D000970:Antineoplastic Agents; D008081:Liposomes; D011720:Pyrazoles; D013449:Sulfonamides; D014810:Vitamin E; D000068579:Celecoxib; C488288:2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy acetic acid; D024505:Tocopherols