Purpose: Investigating the triple effect of doxorubicin, 5-fluorouracil, propranolol on MCF-7 (ER+, WTp53) breast cancer cell line with MTT test and survival analysis. Materials/Methods: In order to determine effectiv...Purpose: Investigating the triple effect of doxorubicin, 5-fluorouracil, propranolol on MCF-7 (ER+, WTp53) breast cancer cell line with MTT test and survival analysis. Materials/Methods: In order to determine effective dosages of a combination of doxorubicin, 5-fluorouracil, propranolol on the MCF-7 cell line by using MTT and survival analysis technique. Result: IC50 values acquired by MTT tests are 0.01 mg/ml for doxorubicin, 6 mg/ml for 5-fluorouracil, 30 mg/ml for propranolol and 0.2/1/30 mg/ml (with previous respect) if all three agents are combined. It is found that the use of doxorubicin, 5-fluorouracil, and propranolol in combination is much effective than their single application. Discussion: Moderate concentrations of doxorubicin, 5-fluorouracil, and propranolol, if they are applied individually, showed high toxicity. When we used these drugs in combination;toxic effects lessened with respect to monotherapy. In the MCF-7 cell line, doxorubicin (IC50: 0.01 μM) increases cell death rates significantly and propranolol (IC50: 3 μM) has minimum effects in monotherapy in contrast to others. Propranolol is only superior to itself in combination therapy (IC50: 4 μM). However 5-fluorouracil (IC50: 30 μM) showed antagonistic effects with respect to other drugs. Additionally, having applied the three drugs in combination on the MCF-7 cell line for the first time in literature, it is highly possible to assess the application of doxorubicin, 5-fluorouracil and propranolol combination as a novel therapy option.展开更多
Purpose: MCF-7 (ER+, WTP53) and MDA-MB-231 (ER Met, Mutant P53) Caffeic Acid Phenethyl Ester (CAPE) and DNA Methyl Transferase Inhibitor (DNMTi) in breast cancer cell lines of Zebularine (ZEB) single and combined appl...Purpose: MCF-7 (ER+, WTP53) and MDA-MB-231 (ER Met, Mutant P53) Caffeic Acid Phenethyl Ester (CAPE) and DNA Methyl Transferase Inhibitor (DNMTi) in breast cancer cell lines of Zebularine (ZEB) single and combined application of TP53, caspase-9, caspase 8 and caspase-3 genes as a result of the use of single and combined drug methylation profiles are aimed to be evaluated by specific PCR method. Material-Metods: In the MCF-7 and MDA-MB-231 breast cancer cell lines, MTT test and survival analysis were performed as a result of single and combined application of CAPE and Zebularine and Methylation Specific PCR was performed to examine the methylation of caspase-3, caspase-8, caspase-9 and TP53 genes. Results: According to the results of 24-hour drug administration, the IC50 for the MCF-7 cell line was determined as 200 μM, for CAPE 40 μM and for the combined values of 50 μM ZEB + 5 μM CAPE. The effects of caspase-3, caspase-8, caspase-9 and TP53 genes on the methylation level of ZEB, CAPE and ZEB + CAPE drug combination were determined by using bisulfite modified DNAs in MCF-7 and MDA-MB-231 cell lines. Discussion: In the MCF-7 cell line, the 120 μM ZEB viability rate was 51%, and the viability of 80 μM ZEB MDA-MB-231 breast cancer cells decreased by 59.7%. After 20 μM CAPE, viability in MCF-7 cells decreased by 31% in 120 μM CAPE and MDA-MB-231 cells decreased by 41%. The viability with 40 μM CAPE decreased by 19% in MDA-MB-231 cells. It was found that 20 μM CAPE concentration was associated with TP53 methylation in MCF-7 cell lines. The 80 μM ZEB concentration was found to be closely related to the unmethylated status of the TP53 gene. These results obtained with 50 μM ZEB + 5 μM CAPE application were found to be related to the methylated-unmetylated status of the TP53 gene in half (50%). For the caspase-9 gene of MDA-MB-231 cells, 80 μM ZEB concentration was found to be associated with unmetylated status. The effective use of drugs with low concentrations of the drug dose provides a more appropriate approach in terms of treatment.展开更多
文摘Purpose: Investigating the triple effect of doxorubicin, 5-fluorouracil, propranolol on MCF-7 (ER+, WTp53) breast cancer cell line with MTT test and survival analysis. Materials/Methods: In order to determine effective dosages of a combination of doxorubicin, 5-fluorouracil, propranolol on the MCF-7 cell line by using MTT and survival analysis technique. Result: IC50 values acquired by MTT tests are 0.01 mg/ml for doxorubicin, 6 mg/ml for 5-fluorouracil, 30 mg/ml for propranolol and 0.2/1/30 mg/ml (with previous respect) if all three agents are combined. It is found that the use of doxorubicin, 5-fluorouracil, and propranolol in combination is much effective than their single application. Discussion: Moderate concentrations of doxorubicin, 5-fluorouracil, and propranolol, if they are applied individually, showed high toxicity. When we used these drugs in combination;toxic effects lessened with respect to monotherapy. In the MCF-7 cell line, doxorubicin (IC50: 0.01 μM) increases cell death rates significantly and propranolol (IC50: 3 μM) has minimum effects in monotherapy in contrast to others. Propranolol is only superior to itself in combination therapy (IC50: 4 μM). However 5-fluorouracil (IC50: 30 μM) showed antagonistic effects with respect to other drugs. Additionally, having applied the three drugs in combination on the MCF-7 cell line for the first time in literature, it is highly possible to assess the application of doxorubicin, 5-fluorouracil and propranolol combination as a novel therapy option.
文摘Purpose: MCF-7 (ER+, WTP53) and MDA-MB-231 (ER Met, Mutant P53) Caffeic Acid Phenethyl Ester (CAPE) and DNA Methyl Transferase Inhibitor (DNMTi) in breast cancer cell lines of Zebularine (ZEB) single and combined application of TP53, caspase-9, caspase 8 and caspase-3 genes as a result of the use of single and combined drug methylation profiles are aimed to be evaluated by specific PCR method. Material-Metods: In the MCF-7 and MDA-MB-231 breast cancer cell lines, MTT test and survival analysis were performed as a result of single and combined application of CAPE and Zebularine and Methylation Specific PCR was performed to examine the methylation of caspase-3, caspase-8, caspase-9 and TP53 genes. Results: According to the results of 24-hour drug administration, the IC50 for the MCF-7 cell line was determined as 200 μM, for CAPE 40 μM and for the combined values of 50 μM ZEB + 5 μM CAPE. The effects of caspase-3, caspase-8, caspase-9 and TP53 genes on the methylation level of ZEB, CAPE and ZEB + CAPE drug combination were determined by using bisulfite modified DNAs in MCF-7 and MDA-MB-231 cell lines. Discussion: In the MCF-7 cell line, the 120 μM ZEB viability rate was 51%, and the viability of 80 μM ZEB MDA-MB-231 breast cancer cells decreased by 59.7%. After 20 μM CAPE, viability in MCF-7 cells decreased by 31% in 120 μM CAPE and MDA-MB-231 cells decreased by 41%. The viability with 40 μM CAPE decreased by 19% in MDA-MB-231 cells. It was found that 20 μM CAPE concentration was associated with TP53 methylation in MCF-7 cell lines. The 80 μM ZEB concentration was found to be closely related to the unmethylated status of the TP53 gene. These results obtained with 50 μM ZEB + 5 μM CAPE application were found to be related to the methylated-unmetylated status of the TP53 gene in half (50%). For the caspase-9 gene of MDA-MB-231 cells, 80 μM ZEB concentration was found to be associated with unmetylated status. The effective use of drugs with low concentrations of the drug dose provides a more appropriate approach in terms of treatment.
