Effects of Ascorbic Acid on Tax, NF-κB and MMP-9 in Human T-cell Lymphotropic Virus Type 1 Positive Malignant T-Lymphocytes

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Authors: Steve Harakeh,*, Jihane Khalife, Elias Baydoun, Rania Azar, Ahmed Al- Hejin, Elie Barbour,
Esam Azhar, Aleksandra Niedzwiecki, Soad Al Jaouni, Mona Diab-Assaf, and Mathias Rath

Journal Name: Anti-Cancer Agents in Medicinal Chemistry, 2017, 17, 000-000

DOI: 10.2174/1871520617666170725160628


HTLV-1 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 HTLV-1-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 lines.

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.

Key words: Acute T-cell leukemia, Human T-cell Lymphotrophic Virus type I (HTLV-1), Tax, NF-κB pathway, Matrix metalloproteinase-9 (MMP-9), Ascorbic Acid (AA).
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