Tocotrienols inhibit growth of ZR-75–1 breast cancer cells

Abstract

The vitamin E component of palm oil provides a rich source of tocotrienols which have been shown previously to be growth inhibitory to two human breast cancer cell lines: responsive MCF7 cells and unresponsive MDA-MB-231 cells. Data presented here shows that the tocotrienol-rich fraction (TRF) of palm oil and individual fractions (alpha, gamma and delta) can also inhibit the growth of another responsive human breast cancer cell line, ZR-75-1. At low concentrations in the absence of oestrogen tocotrienols stimulated growth of the ZR-75-1 cells, but at higher concentrations in the presence as well as in the absence of oestradiol, tocotrienols inhibited cell growth strongly. As for MCF7 cells, a-tocopherol had no effect on growth of the ZR-75-1 cells in either the absence or presence of oestradiol. In studying the effects of tocotrienols in combination with antioestrogens, it was found that TRF could further inhibit growth of ZR-75-1 cells in the presence of tamoxifen (10 -7 M and 10 -8 M). Individual tocotrienol fractions (alpha, gamma, delta) could inhibit growth of ZR-75-1 cells in the presence of 10 -8 M oestradiol and 10 -8 M pure antioestrogen ICI 164 384. The immature mouse uterine weight bioassay confirmed that TRF could not exert oestrogen antagonist action in vivo. These results provide evidence of wider growth-inhibitory effects of tocotrienols beyond MCF7 and MDA-MB-231 cells, and with an oestrogen-independent mechanism of action, suggest a possible clinical advantage in combining administration of tocotrienols with antioestrogen therapy. Int J Food Sci Nutr Downloaded from informahealthcare.com by University of Calgary on 02/02/15 For personal use only. S96 K. Nesaretnam et al.Figure 5. Effect of the tocotrienol-rich fraction (TRF) of palm oil on uterine weight in immature female CD1 mice. Mice were treated with subcutaneous injection of 0.5 ml of ethanol alone (control) (n = 6), of 10 -5 M estradiol in ethanol (+E) (n = 5), of 10 -3 M TRF in ethanol (+TRF) (n = 4) or of both 10 -5 M estradiol in ethanol and 10 -3 M TRF in ethanol (+E+TRF) (n = 3). Error bars indicate the standard error within each treatment group. Int J Food Sci Nutr Downloaded from informahealthcare.com by University of Calgary on 02/02/15 For personal use only.

Tocotrienols are good adjuvants for developing cancer vaccines

“…Previous reports by Nesaretnam and co-workers [12,13,19-21] have shown that tocotrienol on its own can inhibit growth of human breast cancer cells in vitro [12,19] as well as in athymic nude mice [21]. The combination of tumour lysate pulsed-DC and TRF supplementation observed in this study could inhibit the growth of breast tumour in the mouse model.…”

“…Hence, certain nutritional products or supplement may provide a boost for host immune system to fight tumour and this could improve the outcome of treatment. We have previously shown that vitamin E, namely the tocotrienol-rich fraction isolated from palm oil is effective in inhibiting the growth of human mammary cancer cell line in culture [5,12,13]. In this study, investigation on the effects of TRF supplementation, a non-toxic natural compound from palm oil to improve the efficacy of vaccines against breast cancer in our BALB/C mouse model has been carried out.…”

Effectiveness of tocotrienol-rich fraction combined with tamoxifen in the management of women with early breast cancer: a pilot clinical trial

“…However, this was not statistically significant ( P = 0.27). Previous studies carried out in our laboratory showed that tocotrienols inhibited growth and proliferation of breast cancer cells [6-8]. Another study reported that the anticarcinogenic property of tocotrienols in synergy with tamoxifen is more potent than tamoxifen alone [11].…”

“…Because tocotrienols are more potent than tocopherols [6-8,11,12], we hypothesize that tocotrienol intake may be associated with improved survival and lower recurrence in patients with early breast cancer. We investigated the effectiveness of TRF in combination with tamoxifen compared with placebo with tamoxifen as adjuvant therapy in improving breast cancer-specific survival in women with estrogen receptor (ER)-positive tumors who had been treated for TNM stage 1 and stage 2 (early) breast cancer.…”

Activation of the steroid and xenobiotic receptor, SXR, induces apoptosis in breast cancer cells

“…Other compounds such as fatty acid amides and retinoid × receptor (RXR) agonists are also effective against breast cancer in cell lines and in animal models [2,3]. Interestingly, a macrolide antibiotic-rifampicin, the antimycotic drug clotrimazole, endogenous cannabinoids such as anandamide, RXR agonists (rexinoids) such as targretin, and tocotrienol forms of Vitamin E share the ability to inhibit the growth of various types of cancer [2-8]. Some of these compounds such as rifampicin, targretin, and tocotrienols have also been shown to have synergistic or additive effects against cancer when used together with tamoxifen [4,7,9].…”