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The pyrimidine analog FNC inhibits cell proliferation and viral protein synthesis in HTLV‑1‑infected cells
- Source :
- Molecular medicine reports. 7(5)
- Publication Year :
- 2012
-
Abstract
- Human T‑cell leukemia virus type 1 (HTLV‑1), the first retrovirus to be identified, is the etiological agent of an aggressive clonal malignancy of mature CD4+ T lymphocytes known as adult T‑cell leukemia (ATL). The prognosis of ATL patients remains poor despite the availability of a number of clinical chemotherapy drugs. In addition, HTLV‑1‑infected and ATL cells possess an intrinsic resistance to anticancer drugs. 2'‑Deoxy‑2'‑β‑fluoro‑4'‑azidocytidine (FNC) is a novel pyrimidine analog that is efficiently phosphorylated by cellular kinases and is a substrate for RNA and DNA polymerases. In the present study, the antiviral potential of FNC was investigated in HTLV‑1‑infected cell lines. Following FNC treatment, the HTLV‑1‑infected cells underwent G1 or S phase cell cycle arrest. FNC was also observed to reduce cell growth of the HTLV‑1‑infected cell lines in a dose‑dependent manner. Notably, FNC was found to efficiently inhibit the expression of the viral proteins, Tax and p19Gag, in a dose‑ and time‑dependent manner. Treatment with FNC and the protein biosynthesis inhibitor, cycloheximide (CHX), accelerated the inhibition of viral protein synthesis in the HTLV‑1‑infected cells. Collectively, these results demonstrated the efficient antiretroviral effect of FNC in HTLV‑1‑infected cells and indicate that FNC may be utilized as a valuable therapy in HTLV‑1‑infected patients and those with ATL.
- Subjects :
- Cancer Research
Azides
viruses
Cell
Biology
Biochemistry
Deoxycytidine
S Phase
Viral Proteins
Retrovirus
immune system diseases
hemic and lymphatic diseases
Cell Line, Tumor
Genetics
medicine
Humans
Molecular Biology
Cell Proliferation
Human T-lymphotropic virus 1
Oncogene
Cell growth
Cell Cycle
Cell cycle
biology.organism_classification
medicine.disease
Molecular biology
G1 Phase Cell Cycle Checkpoints
HTLV-I Infections
Leukemia
medicine.anatomical_structure
Pyrimidines
Oncology
Cell culture
Protein Biosynthesis
Cancer research
Molecular Medicine
Subjects
Details
- ISSN :
- 17913004
- Volume :
- 7
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Molecular medicine reports
- Accession number :
- edsair.doi.dedup.....aa6b1bc3f4eb4218d46eca3c1f4f830f