Background: HTLV1 is a retrovirus that infects CD4-positive cells and leads to Adult T-cell leukemia
by constitutive activation of nuclear factor kappa B. Ascorbic acid (AA) is an essential nutrient that possess
anti-proliferative and pro-apoptotic activity against a number of malignant cell lines. This study delineates the
effect of AA on Tax protein expression as well as NF-κB and MMP9 activity in two HTLV1-positive leukemia
cells (HuT-102 and C91-PL).
Methods: The cytotoxic and antiproliferative effect of AA were studied by LDH release and MTT tests, respectively.
The proteins expression level was assessed by western blotting. RT-PCR was used to study mRNAs
level. Finally, ELISA/EMSA and Zymography were used to evaluate NF-κB and MMP-9 activities, respectively.
Results: Cell lines were treated with non-cytotoxic concentrations of AA for 48h and 96h, which resulted in a
significant inhibition of proliferation at a concentration of 50µg/ml at 96h in both cell lines. The same concentration
inhibited Tax protein expression as well as the NF-κB nuclearization and DNA binding activity. The
inhibitory effect of AA on MMP9 protein expression and activity started at 100µg/ml and 50µg/ml in HuT-102
and C91-PL cells respectively, with no effect at the transcriptional levels of MMP-9 in either one of the two cell
Conclusion: These results indicated that while AA exerted its anti-proliferative effect on the NF- κB activation
pathway by suppressing Tax expression, its effects on MMP9 seemed to be independent of this mechanism and
follow a different approach.