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

[ Vol. 18 , Issue. 2 ]

Author(s):

Steve Harakeh*, Jihane Khalife, Elias Baydoun, Rania Azar, Ahmed Al- Hejin, Elie Barbour, Esam Azhar, Aleksandra Niedzwiecki, Soad Al Jaouni, Mona Diab-Assaf, Mohammad A. Kamal and Mathias Rath   Pages 237 - 244 ( 8 )

Abstract:


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 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.

Keywords:

Acute T-cell leukemia, Human T-cell Lymphotrophic Virus type I (HTLV1), Tax, NF-κB pathway, Matrix metalloproteinase-9 (MMP-9), Ascorbic Acid (AA), antipoliferative effect.

Affiliation:

Special Infectious Agents Unit, King Fahd Medical Research Center; Yousef Abdullatif Jameel Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University (KAU) Jeddah 21589, Biology Department, American University of Beirut (AUB), Biology Department, American University of Beirut (AUB), Lebanese University, EDST ("Molecular Tumor-genesis and Anticancer Pharmacology"), Hadath, Biology Department, King Abdulaziz University P.O.Box: 80216, Jeddah 21589, Department of Agriculture, Faculty of Agricultural and Food Sciences, American University of Beirut, Beirut, Special Infectious Agents Unit, King Fahd Medical Research Center; Yousef Abdullatif Jameel Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University (KAU) Jeddah 21589, Dr. Rath Research Institute, Santa Clara, CA, Department of Pediatric Hematology/Oncology, KAU, Lebanese University, EDST ("Molecular Tumor-genesis and Anticancer Pharmacology"), Hadath, King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Jeddah 21589, Dr. Rath Research Institute, Santa Clara, CA

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