Abstract:
INTRODUCTION:The reason for unsuccessful tumor chemotherapy is related to multidrug resistance. An important factor is the overexpression of efflux pumps, such as P-glycoprotein. AIM:Amino- and amide-substituted steroid compounds and phenothiazine derivatives were investigated in tumor models in vitro. METHOD:The inhibition of P-glycoprotein was evaluated by flow cytometry and the interaction of these compounds with doxorubicin was investigated as well. Molecular docking was used to estimate the binding energies of the compounds to P-glycoprotein. RESULTS:The aminosteroids showed anticancer activity on multidrug resistant mouse T-lymphoma and prostate cancer cell lines. The combination of steroids and doxorubicin potentiated its effect in hormone resistant prostate cancer cells. Among the N-hydroxyalkyl-2-aminophenothiazines, secondary amines exhibited anticancer effects on multidrug resistant colon adenocarcinoma cells. CONCLUSIONS:The tested phenothiazine and steroid derivatives showed potent anticancer activity, furthermore, the stereoisomerism of thioridazine did not play a role in the antitumor properties. Neither steroids nor thioridazine influenced apoptosis in hormone resistant cells. Orv. Hetil., 2016, 157(37), 1489-1495.
journal_name
Orv Hetiljournal_title
Orvosi hetilapauthors
Csonka Ádoi
10.1556/650.2016.30536subject
Has Abstractpub_date
2016-09-01 00:00:00pages
1489-95issue
37eissn
0030-6002issn
1788-6120journal_volume
157pub_type
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