[Comparison of the effect of multidrug resistance modifiers on prostate cancer, mouse lymphoma and colon cancer cells].
BACKGROUND
The reason for unsuccessful tumor chemotherapy is related to multidrug resistance. An important factor is the overexpression of efflux pumps, such as P-glycoprotein.


OBJECTIVE
Amino- and amide-substituted steroid compounds and phenothiazine derivatives were investigated in tumor models in vitro.


METHODS
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.
Orvosi Mikrobiológiai és Immunbiológiai Intézet, Szegedi Tudományegyetem, Általános Orvostudományi Kar Szeged, Semmelweis u. 6., 6725.
Ákos
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Csonka
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D016399:Lymphoma, T-Cell / Q000188:drug therapy*; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000188:drug therapy*
D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents
ABCB1 transporter; ABCB1-transzporter; cancer cell lines; fenotiazinok; multidrog-rezisztencia; multidrug resistance; phenothiazines; substituted steroids; szubsztituált szteroidok; tumorsejtvonalak