Title:Anti-neoplastic and Calcium modulatory action of Caffeic acid phenethyl ester and Dasatinib in C6 glial cells: A Therapeutic Perspective
Volume: 15
Issue: 1
Author(s): Henah M. Balkhi, Taseen Gul and Ehtishamul Haq
Affiliation:
Keywords:
Glioma, CAPE, dasatinib, combinational therapy, wrights stain, clonogenicity, catalase, and griess assay, atomic
absorption spectroscopy.
Abstract: Gliomas are often recognized as highly heterogeneous cancerous phenotype. They are
perpetually recurrent, obstinately resistant to treatment and hence almost incurable. Drug development
studies to date have revealed only modest effect in attenuating growth of these tumors. The present
study was aimed at elucidating the potential of targeting glioma through a novel combination of drugs
in comparison to single agent. Here, we show that the combined administration of Caffeic acid
phenethyl ester [CAPE] and Dasatinib exerts a strong antitumor action on C6 glioma cells.
Combinational treatment inhibits proliferation, induces apoptosis, modulates astrocytic phenotype and
decreases cell density. Results suggest that combinational therapy inhibits migration and invasiveness, decreases cell
survival fraction and hence clonogenic property of C6 cells. The Nitric oxide [NO] levels were significantly reduced by
combination treatment at all time points and effect was persistent over the time in comparison to single drug treatment.
Atomic Absorption Spectroscopy [AAS] analysis of intracellular and extracellular calcium revealed that the treatment
with CAPE and Dasatinib strongly modulates the calcium [Ca2+] levels. Herein, we demonstrate that treatment of C6
glioma cells with CAPE and Dasatinib significantly decrease the activity of catalase [CAT]. The results in totality suggest
that the combinational therapy remarkably reduces the proliferation of glioma cells possibly through different
mechanisms, targeting multiple pathways involved in tumor growth, proliferation and development implicating the
relevance of using these drugs in combination therapy for effective treatment of glioma. In vitro results suggest that CAPE
and Dasatinib cotreatment could be therapeutically exploited for the management of gliomas.
