Investigation of the effects of alpha-TEA, MSA and t-RES alone and in combination on human MDA-MB-435 breast cancer cells in vitro and in vivo

by 1979- Snyder, Rachel Marie

Alpha-tocopherol ether analog (?-TEA) is a novel form of vitamin E that is effective at killing cancer cells but not normal cells. ?-TEA alone and together with methylseleninic acid (MSA) and trans-resveratrol (t-RES) were investigated for ability to induce apoptosis, DNA synthesis arrest, and cellular differentiation, and inhibit colony formation in human MDA-MB-435-F-L breast cancer cells in culture. The three agents alone were effective in inhibiting cell growth by apoptosis, DNA synthesis arrest, cellular differentiation, and reducing colony formation. Combination treatments synergistically inhibited cell proliferation in the four different assays conducted, in comparison to individual treatments. For induction of apoptosis, enhanced levels of apoptosis were also found using human breast (MDA-MB-231, MCF7, and T47D) and human prostate (LNCaP, PC-3, and DU-145) cancer cell lines, as well as in immortalized but non tumorigenic MCF10A cells. No apoptosis was seen in primary cultures of human mammary epithelial cells (HMECs). Western immunoblotting confirmed that all three compounds individually and in combination induced poly(ADP-ribose) polymerase cleavage with more complete cleavage seen in the combination treatment. In studies of DNA synthesis arrest, clonegenic, and cell differentiation assays, all three compounds produced dose-dependent responses individually and enhanced responses in combination. In summary, the combination of ?-TEA, MSA, and t-RES is more effective than single treatments for inhibiting cell proliferation, and inducing differentiation and apoptosis of human cancer cells in culture. 37