gamma-Tocotrienol controls proliferation, modulates expression of cell cycle regulatory proteins and up-regulates quinone reductase NQO2 in MCF-7 breast cancer cells.
BACKGROUND
Tocotrienols, a subgroup of the vitamin E family, have demonstrated antioxidant and anticancer properties. Differential growth responses among different types of tocotrienols have been observed in breast cancer cells; however, specific bioactivity of each individual tocotrienol remains to be elucidated.


METHODS
In this study, the effects of gamma-tocotrienol were examined with regard to its ability to suppress cell proliferation via modulation of cell cycle regulatory protein expression, and also from the perspective of control of cellular oxidoreductive status through regulation of detoxification enzymes, e.g., quinone reductase NQO2, using estrogen receptor-positive MCF-7 human breast cancer cells.


RESULTS
It was shown that treatment by gamma-tocotrienol suppressed MCF-7 cell proliferation in a dose- and time-dependent manner. Growth suppression by gamma-tocotrienol was accompanied by changes in the levels of cell cycle regulatory proteins, notably, Rb/E2F complex, cyclin D1/cdk4 and cyclin B1/cdk1, as exemplified by loss of cyclin D1, inhibition of specific Rb phosphorylation (pRb-p at Thr821), and by the time- and dose-dependent increase in the expression of NQO2.


CONCLUSIONS
By exerting control on expression of specific cell cycle regulatory proteins in concomitance with suppression of cell proliferation, as well as the induction of NQO2, gamma-tocotrienol offers promise as an added chemopreventive and/or chemotherapeutic agent against breast cancer carcinogenesis.
Hsieh
Tze-Chen
TC
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
Elangovan
Selvakumar
S
Wu
Joseph M
JM
D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002839:Chromans / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D011808:Quinone Reductases / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D018797:Cell Cycle Proteins; D002839:Chromans; D014810:Vitamin E; C013649:plastochromanol 8; C419642:NRH - quinone oxidoreductase2; D011808:Quinone Reductases