Abstract:
:In our endeavour towards the development of effective anticancer therapeutics, a novel series of isoxazole-piperazine hybrids were synthesized and evaluated for their cytotoxic activities against human liver (Huh7 and Mahlavu) and breast (MCF-7) cancer cell lines. Within series, compounds 5l-o showed the most potent cytotoxicity on all cell lines with IC50 values in the range of 0.3-3.7 μM. To explore the mechanistic aspects fundamental to the observed activity, further biological studies with 5m and 5o in liver cancer cells were carried out. We have demonstrated that 5m and 5o induce oxidative stress in PTEN adequate Huh7 and PTEN deficient Mahlavu human liver cancer cells leading to apoptosis and cell cycle arrest at different phases. Further analysis of the proteins involved in apoptosis and cell cycle revealed that 5m and 5o caused an inhibition of cell survival pathway through Akt hyperphosphorylation and apoptosis and cell cycle arrest through p53 protein activation.
journal_name
J Enzyme Inhib Med Chemjournal_title
Journal of enzyme inhibition and medicinal chemistryauthors
Çalışkan B,Sinoplu E,İbiş K,Akhan Güzelcan E,Çetin Atalay R,Banoglu Edoi
10.1080/14756366.2018.1504041subject
Has Abstractpub_date
2018-12-01 00:00:00pages
1352-1361issue
1eissn
1475-6366issn
1475-6374journal_volume
33pub_type
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