Title:N6-Isopentenyladenosine and its Analogue N6-Benzyladenosine Induce Cell Cycle Arrest and Apoptosis in Bladder Carcinoma T24 Cells
Volume: 13
Issue: 4
Author(s): Sara Castiglioni, Silvana Casati, Roberta Ottria, Pierangela Ciuffreda and Jeanette A.M. Maier
Affiliation:
Keywords:
Actin, Apoptosis, Bladder carcinoma cells, Caspase 3, Cell cycle, Cell density, Comet assay, Cytokinin, Cytoskeleton,
Cytotoxicity, Genotoxicity, N6-benzyladenine, N6-benzyladenosine, N6-isopentenyladenosine
Abstract: Cytokinins are phytohormones critically involved in the regulation of plant growth and development. They also affect the
proliferation and differentiation of animal cells, thus representing new tools to treat diseases that involve dysfunctional cell growth and/or
differentiation. Recently, by performing structure-function studies on human cells, we found that only N6-isopentenyladenosine and its
benzyl analogue N6-benzyladenosine suppress the clonogenic activity and the growth of different neoplastic cells. We here broaden our
studies on bladder carcinoma T24 cells, because, due to the high recurrence rate of bladder cancer, new active molecules are sought to
contrast the growth of this tumor. Early events induced by N6-isopentenyladenosine and N6-benzyladenosine are the alteration of T24
cell morphology and the disorganization of the actin cytoskeleton. After 24 h N6-isopentenyladenosine and N6-benzyladenosine inhibit
growth by arresting the cells in the G0/G1 phase of the cell cycle. We also show that the two compounds induce apoptosis, an event
linked to the activation of caspase 3. Since DNA damage is a prime factor resulting in cell cycle arrest and apoptosis, it is noteworthy that
we do not detect any genotoxic effect upon treatment of T24 cells with N6-isopentenyladenosine and N6- benzyladenosine.
Because the disruption of actin filaments leads to G1 arrest and is also implicated in apoptosis, we hypothesize that cytoskeletal
rearrangement might be responsible for triggering the antiproliferative and proapotpotic effects of N6-isopentenyladenosine and N6-
benzyladenosine in T24 cells.
