Blood cancers

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

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

Abstract: 

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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Antineoplastic effects of nutrient mixture on raji and jurkat T cells: the two highly aggressive Non-Hodgkin's Lymphoma cell lines

Roomi MW, Bhananp BA, Roomi NW, Rath M, Niedzwiecki A
Experimental Oncology 2009; 31(3): 149-155

Abstract:
Non-Hodgkin lymphomas incidence has increased more than 70% in last 25 years. Aggressiveness, higher relapse rate, and treatment complications pose significant barriers. Decreased food intake and side effects of treatments make cancer patients vulnerable to deficiency of essential nutrients such as vitamin C, lysine, and proline leading to the formation of weak extra cellular matrix susceptible to easy breakdown by matrix metalloproteinase enzymes.…

Read more: Antineoplastic effects of nutrient mixture on raji and jurkat T cells: the two highly aggressive Non-Hodgkin's Lymphoma cell lines

Epigallocatechin-3-gallate Inhibits Tax-dependent Activation of Nuclear Factor Kappa B and of Matrix Metalloproteinase 9 in Human T-cell Lymphotropic Virus-1 Positive Leukemia Cells.

Steve Harakeh, Mona Diab-Assaf, Rania Azar, Hani Mutlak Abdulla Hassan, Safwan Tayeb, Khalil Abou-El-Ardat, Ghazi Abdullah Damanhouri, Ishtiaq Qadri, Adel Abuzenadah, Adeel Chaudhary, Taha Kumosani, Aleksandra Niedzwiecki, Mathias Rath, Haitham Yacoub, Esam Azhar, Elie Barbour
Asian Pacific journal of cancer prevention: APJCP (Impact Factor: 1.27). 01/2014; 15(3):1219-1225.

Abstract:
Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol molecule from green tea and is known to exhibit antioxidative as well as tumor suppressing activity. In order to examine EGCG tumor invasion and suppressing activity against adult T-cell leukemia (ATL), two HTLV-1 positive leukemia cells (HuT-102 and C91- PL) were treated with non-cytotoxic concentrations of EGCG for 2 and 4 days.…

Read more: Epigallocatechin-3-gallate Inhibits Tax-dependent Activation of Nuclear Factor Kappa B and of Matrix Metalloproteinase 9 in Human T-cell Lymphotropic Virus-1 Positive Leukemia Cells.

Apoptosis induction by Nurient Synergy in HTLV-1 positive and negative malignant T-cells

S. Harakeh, M. Diab-Assaf, A. Niedzwiecki, J. Khalife, K. Abu-El-Ardat, M. Rath
Leukemia Research 2006, 30: 869-881

Introduction:
Human T-cell lymphotropic virus type-1 (HTLV-1) is the causative agent of adult T-cell leukemia, a fatal disease with average survival time of less than one year. A novel nutrient formulation, Nutrient Synergy (NS), which contains lysine, proline, ascorbic acid, and green tea extract, has been shown to be effective in inhibiting cell invasion, proliferation and angiogenesis of various solid cancers.…

Read more: Apoptosis induction by Nurient Synergy in HTLV-1 positive and negative malignant T-cells

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

S. Harakeh, M. Diab-Assaf, K. Abu-El-Ardat, A. Niedzwiecki, M. Rath
Chemico-Biological Interactions 2006, 164: 102-114

Abstract:
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.…

Read more: Mechanistic aspects of apoptosis induction by L-lysine in both HTLV-1-positive and -negative cell lines