Abstract
The effects of a specific nutrient synergy (SNS), consisting of a combination of antioxidants, vitamins and amino-acids (three of its major components being ascorbic acid (AA), epigallocatechin gallate (EGCG) and L-lysine) were investigated on proliferation and induction of apoptosis using non-cytotoxic concentrations against HTLV-I-positive and -negative malignant T-cells. In addition, the effects of SNS, AA, EGCG and L-lysine were evaluated on the activity, transcriptional and translational levels of the two important gelatinases, metalloproteinases-2 and -9, as Well as on the NF- Kappa B pathway and Tax production in HTLV-I-positive cell lines. The results indicated that the SNS had a more potent anti-proliferative effect than its individual ingredients and more pronounced induction of apoptosis in both HTLV-I-positive and -negative malignant T-cells. The SNS also inhibited extravasation by significantly down-regulating MMP-2 and -9 activity, production and expression as was shown by zymography, Western blotting and RT-PCR. Moreover, the SNS inhibited the translocation of the p65/p50 subunits to the nucleus in a dose-dependent manner as well as Tax production in HTLV-I-positive malignant T-cell lines. In conclusion, the results indicate that the SNS could constitute a potential anti-invasive treatment in adult T-cell leukemia and related diseases. Based on the effectiveness of the SNS in targeting common critical mechanisms involved in cancer and its minimal cell toxicity, as compared to pharmaceutical drugs, clinical investigations are highly recommended.