Mechanistic aspects of apoptosis induction by L-lysine in both HTLV-1-positive and -negative cell lines

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S. Harakeh, M. Diab-Assaf, K. Abu-El-Ardat, A. Niedzwiecki, M. Rath
Chemico-Biological Interactions 2006, 164: 102-114

The retrovirus human T-cell lymphotrophic virus type-1 (HTLV-1) causes adult T-cell leukemia (ATL), which remains with no cure. This study evaluates the effects of L-lysine on proliferation and induction of apoptosis using non-cytotoxic concentrations of the test compound against HTLV-1 positive and negative malignant cell lines.

The anti-proliferative effect of lysine was established and confirmed by studying the effects of the test compound on the expression of TGF mRNA expression by RT-PCR. To investigate the effect of L-lysine on the induction of apoptosis, DNA flow sytometry analyses was done and the results verified by cell death ELISA. The results indicated that a significant increase in the preG1 phase and a decrease in the s phase of the cell cycle in all of the ATL cells tested. L-lysine up-regulated p53, p21, and Bax protein levels and a down-regulation of Bel-2a in all the cell lines tested. L-lysine was found to exert its effect through the NF-kB pathway by inhibiting the p65 subunit specifically. Also L-lysine caused a decrease in the levels MMP-2 and MMP-9 as well as their enzymatic activity.

Key Words:
Apoptosis, HTLV-1, L-lysine, Adult T-cell leukemia

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