Blood Cancer

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).
Access:

 

 

Effect Of A Nutrient Mixture On Fanconi Anemia Fibroblast And Normal Human Dermal Fibroblast: A Comparison

M.W. Roomi, T. Kalinovsky, A. Niedzwiecki and M. Rath
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
Open Journal of Apoptosis 5:2-8, 2016

Abstract: 

Fanconi anemia (FA) is a fatal heterogeneous autosomal recessive disorder, characterized by progressive bone marrow failure, congenital defect and cancer predisposition. Cell culture from FA fibroblast (FAF) displays certain abnormalities as compared to normal human dermal fibroblast (NHDF). This prompted us to investigate the effect of a novel nutrient mixture (NM) containing ascorbic acid, lysine, proline and green tea extract, which has demonstrated a broad spectrum of pharmacological activities, on FAF compared to NHDF.

Read more ...

In vitro inhibition of matrix metalloproteinases, invasion and growth of Fanconi anemia human FANCA and FANCC lymphoblasts by nutrient mixture

Roomi MW,Bhanap B, Roomi NW, Niedzwiecki A, Rath M.

Exp Oncol.2014;36(3):212-4.

Abstract: 

Aim: Fanconi anemia is a rare genetic disorder with high propensity for development of cancers, such as aplastic anemia, leukemia and head and neck cancers. Collagen digesting matrix metalloproteinase (MMP) enzymes have been implicated in for their role in various malignancies and to promote metastasis.

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.

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 ...

Repression of matrix metalloproteinases and inhibition of cell invasion by a nutrient mixture, containing ascorbic acid, lysine, proline, and green tea extract on human Fanconi anemia fibroblast cell lines

Roomi MW,Bhanap B, Roomi NW, Niedzwiecki A, Rath M.

ExpOncol. 2013; 35(1):20-24.

Abstract:

Aim: Fanconi Anemia, an autosomal recessive disorder, is characterized by chromosomal abnormality leading to birth defects, progressive bone marrow failure, and a high probability of developing malignancy at an early age. Head and neck squamous cell carcinoma and myeloid leukemia are the major causes of cancer related morbidity and mortality in Fanconi anemia patients.

Read more ...