N-(2-hydroxyphenyl)acetamide (NA-2) and Temozolomide synergistically induce apoptosis in human glioblastoma cell line U87.

Cancer Cell Int

Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270 Pakistan ; H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270 Pakistan.

Published: February 2015

Background: Despite the modern therapies available for treating glioblastoma multiforme (GBM), it is still a deadly disease. The development of new therapeutic strategies for the management of gliomas is therefore crucial. The present study is designed to analyze the therapeutic potentials of synthetic compound N-(2-hydroxyphenyl)acetamide (NA-2) in the treatment of GBM as a single agent or in combination with Temozolomide (TMZ) on glioblastoma cells.

Methods: MTT and TUNEL assays were used to detect the growth inhibitory effect and apoptotic activity of NA-2 alone and in combination with TMZ. Synergy was assessed using combination Index method. The expression of apoptosis related markers Bax, Bcl-2 and caspase-3 were assessed by RT-PCR, whereas, the active caspase-3 protein expression was determined using imunocytochemistry.

Results: Both NA-2 and TMZ inhibited the growth of U87 in a dose dependent manner. The combine administration of NA-2 (0.33 mM) and temozolomide (0.1 mM) significantly enhanced the cell growth inhibition and apoptosis. Furthermore RT-PCR and imunocytochemistry data revealed that cooperative apoptosis induction was associated with increased ratio of Bax to Bcl-2 and active Caspase-3 expression.

Conclusion: Our findings support that NA-2 possesses strong apoptotic activity and the combined administration of NA-2 and TMZ may be therapeutically exploited for the management of GBM.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319240PMC
http://dx.doi.org/10.1186/s12935-014-0133-5DOI Listing

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