Antiproliferative Activity of α-Tocopherol, γ-Tocopherol and Tocotrienols and Their Drug Interactions Evaluated Using Loewe and Chou–Talalay Models in HeLa and MCF-7 Cancer Cell Lines

Background: Food rich in tocopherols (T) and tocotrienols (T3) are considered functional due to their ability to reduce oxidative stress and modulate anti-viability and pro-apoptotic pathways with anticancer potential; however, their efficacy differs between T and T3 and among isoforms (α and γ) likely due to differences in intracellular uptake and, consequently, in the activation of anticancer signaling pathways. To address these isoform-dependent differences, HeLa and MCF7 cancer cell lines were used to assess the antiproliferative activity of α-tocopherol (αT), γ-tocopherol (γT) and tocotrienols (Tocomin) as well as their pharmacological interactions according to Loewe and Chou–Talalay models. Methods: The tocol profile of the commercial mixture of T3 (Tocomin) was quantified by normal-phase HPLC. HeLa, MCF7, and ARPE-19 cells were cultured in DMEM supplemented with 10% FBS and exposed to αT, γT, or Tocomin (50–800 µg/mL; DMSO vehicle) for 48 h; viability was measured by the MTT assay and EC50 values were obtained from log(dose)–response fits (n = 3). Fixed-ratio (1:1) combinations were evaluated in HeLa and MCF7, and interactions were quantified using Loewe additivity and Chou–Talalay combination indices, supported by isobologram analysis. Results: Tocomin showed greater potency with αT and γT, and synergy with αT/γT; however, the combination of αT + γT showed antagonism in both cell lines. Conclusions: The higher potency of Tocomin and its synergistic interactions with αT or γT suggest that tocotrienol-rich mixtures may enhance the antiproliferative response, whereas combining αT and γT together may reduce efficacy under the tested conditions.