Research: BAK and COLLEAGUES,

Listed in Issue 270

Abstract

BAK and COLLEAGUES, 1. Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey; 2. Department of Food Science and Technology, Chung-Ang University, Anseong, South Korea; 3. Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey; 4. Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey. nsuh@pharmacy.rutgers.edu  studied the effect of different forms of tocopherols in oestrogen-mediated breast cancer.

Background

Oestrogens have been implicated as complete carcinogens for breast and other tissues through mechanisms involving increased cell proliferation, oxidative stress, and DNA damage.

Methodology

Because of their potent antioxidant activity and other effects, tocopherols have been shown to exert antitumor activities in various cancers. However, limited information is available on the effect of different forms of tocopherols in oestrogen-mediated breast cancer. To address this, we examined the effects of α-, γ-, and δ-tocopherols as well as a natural γ-tocopherol-rich mixture of tocopherols, γ-TmT, on oestrogen-stimulated MCF-7 cells in vitro and in vivo For the in vivo studies, MCF-7 cells were injected into the mammary fat pad of immunodeficient mice previously implanted with oestrogen pellets. Mice were then administered diets containing 0.2% α-, γ-, δ-tocopherol, or γ-TmT for 5 weeks.

Results

Treatment with α-, γ-, δ-tocopherols, and γ-TmT reduced tumour volumes by 29% (P < 0.05), 45% (P < 0.05), 41% (P < 0.05), and 58% (P < 0.01), as well as tumour weights by 20%, 37% (P < 0.05), 39% (P < 0.05), and 52% (P < 0.05), respectively. γ- and δ-tocopherols and γ-TmT inhibited the expression of cell proliferation-related genes such as cyclin D1 and c-Myc, and oestrogen-related genes such as TFF/pS2, cathepsin D, and progesterone receptor in oestrogen-stimulated MCF-7 cells in vitro. Further, γ- and δ-tocopherols decreased the levels of oestrogen-induced oxidative stress and nitrosative stress markers, 8-hydroxy-2'-deoxyguanosine and nitro tyrosine, as well as the DNA damage marker, γ-H2AX.

Conclusion

Our results suggest that γ- and δ-tocopherols and the γ-tocopherol-rich mixture are effective natural agents for the prevention and treatment of oestrogen-mediated breast cancer.

References

Bak MJ1, Das Gupta S1, Wahler J1, Lee HJ2, Li X1, Lee MJ1, Yang CS1,3, Suh N4,3. Inhibitory Effects of γ- and δ-Tocopherols on Estrogen-Stimulated Breast Cancer In Vitro and In Vivo. Cancer Prev Res (Phila). 10(3):188-197. Mar 2017. doi: 10.1158/1940-6207.CAPR-16-0223. Epub Jan 17 2017.

Comment

The above research demonstrated that γ-, δ-tocopherols and the γ-tocopherol-rich mixture led to reduced tumour volumes and weights and inhibited expression of cell-proliferation-related genes, as well as oestrogen-induced oxidative stress and DNA damage marker, suggesting that these tocopherols may be natural effective agents in the prevention and treatment of oestrogen-mediated breast cancer.

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