α-Tocopheryloxyacetic acid is superior to α-tocopheryl succinate in suppressing HER2-high breast carcinomas due to its higher stability.
Breast cancer is the number one neoplastic disease of women, with the HER2-high carcinomas presenting a considerable challenge for efficient treatment. Therefore, a search for novel agents active against this type of cancer is warranted. We tested two vitamin E (VE) analogs, the esterase-hydrolyzable α-tocopheryl succinate (α-TOS) and the non-hydrolyzable ether α-tocopheryloxyacetic acid (α-TEA) for their effects on HER2-positive breast carcinomas using a breast tumor mouse model and breast cancer cell lines. Ultrasound imaging documented that α-TEA suppressed breast carcinomas in the transgenic animals more efficiently than found for its ester counterpart. However, both agents exerted a comparable apoptotic effect on the NeuTL breast cancer cells derived from the FVB/N c-neu mice as well as in the human MBA-MD-453 and MCF7HER2-18 cells with high level of HER2. The superior anti-tumor effect of α-TEA over α-TOS in vivo can be explained by longer persistence of the former in mice, possibly due to the enhanced plasma and hepatic processing of α-TOS in comparison to the esterase-non-cleavable α-TEA. Indeed, the stability of α-TOS in plasma was inferior to that of α-TEA. We propose that α-TEA is a promising drug efficient against breast cancer, as documented by its effect on experimental HER2-positive breast carcinomas that present a considerable problem in cancer management.
School of Medical Science, Griffith Health Institute, Griffith University, Southport, QLD, Australia. l.dong@griffith.edu.au
Lan-Feng
LF
Dong
Gary
G
Grant
Helen
H
Massa
Renata
R
Zobalova
Emmanuel
E
Akporiaye
Jiri
J
Neuzil
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D017382:Reactive Oxygen Species / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D024505:Tocopherols / Q000737:chemistry* / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D024502:alpha-Tocopherol / Q000737:chemistry* / Q000627:therapeutic use*
D000975:Antioxidants; D017382:Reactive Oxygen Species; D018719:Erb-b2 Receptor Tyrosine Kinases; D024505:Tocopherols; D024502:alpha-Tocopherol; C488288:2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy acetic acid