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Evaluation of anticancer effects of newly synthesized dihydropyridine derivatives in comparison to verapamil and doxorubicin on T47D parental and resistant cell lines in vitro

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Evaluation of anticancer effects of newly synthesized dihydropyridine derivatives in comparison to verapamil and doxorubicin on T47D parental and resistant cell lines in vitro

Content Provider	Springer Nature Link
Author	Bazargan, L. Fouladdel, S. Shafiee, A. Amini, M. Ghaffari, S. M. Azizi, E.
Copyright Year	2007
Abstract	Failure of current anticancer drugs mandates screening for new compounds of synthetic or biological origin to be used in cancer therapy. Multidrug resistance (MDR) is one of the main obstacles in the chemotherapy of cancer. Efflux of cytotoxic agents mediated by P-glycoprotein (P-gp or MDR1) is believed to be an important mechanism of multidrug resistance. Therefore, we decided to investigate the antiproliferative effects of seven newly synthesized 1,4-dihydropyridine (DHP) derivatives in comparison to verapamil (VP) and doxorubicin (DOX) on human breast cancer T47D cells and its MDR1 overexpressed and moderately resistant cells (RS cells) using MTT cytotoxicity assay. We also examined the effects of these compounds on cytotoxicity of DOX in these two cell types. The cytotoxicity assays using MTT showed that most of the tested new DHP derivatives and VP at 10 μM concentration had varying levels of toxicity on both T47D and RS cells. The toxicity was mostly in the range of 10–25%. However, the cytotoxicity of these DHP derivatives, similar to VP, was significantly less than DOX when comparing IC50 values. Furthermore, these compounds in general had relatively more cytotoxicity on T47D vs RS cells at 10-μM concentration. Among new DHPs, compounds 7a (3,5-dibenzoyl-4-(2-methylthiazol-4-yl)-1,4-dihydro-2,6-dimethylpyridine) and 7d (3,5-diacetyl-4-[2-(2-chlorophenyl)thiazol-4-yl)]-1,4-dihydro-2,6-dimethylpyridine) showed noticeable potentiation of DOX cytotoxicity (reduction of DOX IC50) compared to DOX alone in both cells, particularly in RS cells. This effect was similar to that of VP, a known prototype of MDR1 reversal agent. In other words, compounds 7a and 7d resensitized RS cells to DOX or reversed their resistance. Results indicate that compound 7d exerts highest effect on RS cells. Therefore, these two newly synthesized DHP derivatives, compounds 7a and 7d, are promising as potential new MDR1 reversal agents and should be further studied on other highly resistant cells due to MDR1 overexpression and with further molecular investigation.
Starting Page	165
Ending Page	174
Page Count	10
File Format	PDF
ISSN	07422091
Journal	Cell Biology and Toxicology
Volume Number	24
Issue Number	2
e-ISSN	15736822
Language	English
Publisher	Springer Netherlands
Publisher Date	2007-09-06
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Anticancer effects Breast cancer 1,4-Dihydropyridines T47D cells Multidrug resistance Biochemistry Pharmacology/Toxicology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Health, Toxicology and Mutagenesis Toxicology

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