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  • Star-shaped tetraspermine enhances cellular uptake and cytotoxicity of T-oligo in prostate cancer cells.

Star-shaped tetraspermine enhances cellular uptake and cytotoxicity of T-oligo in prostate cancer cells.

Pharmaceutical research (2014-08-06)
Vidula Kolhatkar, Hiren Khambati, Asawari Lote, Peter Shanine, Thomas Insley, Soumyo Sen, Gnanasekar Munirathinam, Petr Král, Rohit Kolhatkar
ABSTRACT

An oligonucleotide termed 'T-oligo' having sequence homology with telomere overhang has shown cytotoxicity in multiple cancers. We have demonstrated that T-oligo can induce apoptosis in androgen independent prostate cancer cell line DU-145. In this report, we evaluate the use of star-shaped tetraspermine (SSTS) for delivery of T-oligo. SSTS was synthesized from spermine and its intrinsic cytotoxicity towards DU-145 cells was compared with spermine and branched polyethyleneimine (bPEI). Atomistic molecular dynamic (MD) simulations were conducted to understand binding and complexation of spermine and SSTS with T-oligo. Complexation was also determined using gel electrophoresis and SYBR gold assay. Complexes were characterized for size, cellular uptake and antiproliferative effect. SSTS exhibited significantly lower toxicity than spermine and bPEI. Its affinity towards T-oligo was significantly higher than spermine as determined by experimental studies and confirmed by MD simulations and it formed stable complexes (TONPs) with T-oligo. TONPs facilitated cellular uptake and nuclear accumulation of T-oligo and their cytotoxic potential was observed at concentration several folds lower than that required for T-oligo alone. SSTS significantly enhanced therapeutic benefits associated with the use of T-oligo and can be developed as a delivery vehicle for its in-vivo therapeutic applications.

MATERIALS
Product Number
Brand
Product Description

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