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

Chem Biol Interact. 2006 Dec 1;164(1-2):102-14. doi: 10.1016/j.cbi.2006.09.005. Epub 2006 Sep 16.


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 cytometry analyses was done and the results verified by cell death ELISA. The results indicated that a significant increase in the preG(1) 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 Bcl-2alpha in all the cell lines tested. l-Lysine was found to exert its effect through the NF-kappaB 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.

MeSH terms

  • Adult
  • Apoptosis / drug effects*
  • Base Sequence
  • Cell Cycle / drug effects*
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • DNA / metabolism
  • Dose-Response Relationship, Drug
  • Human T-lymphotropic virus 1 / drug effects*
  • Human T-lymphotropic virus 1 / immunology
  • Humans
  • Lysine / toxicity*
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • NF-kappa B / metabolism
  • RNA, Messenger / metabolism
  • Transcription Factor RelA / antagonists & inhibitors
  • Transforming Growth Factors / genetics
  • Transforming Growth Factors / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein / metabolism
  • bcl-X Protein / metabolism


  • BCL2L1 protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • NF-kappa B
  • RNA, Messenger
  • Transcription Factor RelA
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • Transforming Growth Factors
  • DNA
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Lysine