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

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

Volume: 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

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,Saudi Arabia

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.

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.

Cite this article as:

Harakeh Steve *, Khalife Jihane , Baydoun Elias , Azar Rania , Al- Hejin Ahmed , Barbour Elie , Azhar Esam , Niedzwiecki Aleksandra, Al Jaouni Soad , Diab-Assaf Mona , Kamal A. Mohammad and Rath Mathias, Effects of Ascorbic Acid on Tax, NF-κB and MMP-9 in Human T-cell Lymphotropic Virus Type 1 Positive Malignant T-Lymphocytes, Anti-Cancer Agents in Medicinal Chemistry 2018; 18 (2) . https://dx.doi.org/10.2174/1871520617666170725160628