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Effects of monensin liposomes on the cytotoxicity, apoptosis and expression of multidrug resistance genes in doxorubicin-resistant human breast tumour (MCF-7/dox) cell-line.
J Pharm Pharmacol. 2004 Jul; 56(7):899-907.JP

Abstract

We have evaluated the effects of monensin liposomes on drug resistance reversal, induction of apoptosis and expression of multidrug resistance (MDR) genes in a doxorubicin-resistant human breast tumour (MCF-7/dox) cell line. Monensin liposomes were prepared by the pH-gradient method. MCF-7/dox cells were treated with various anticancer drugs (doxorubicin, paclitaxel and etoposide) alone and in combination with monensin liposomes. The cytotoxicity was assessed using the crystal violet dye uptake method. The induction of apoptosis in MCF-7/dox cells was assessed by established techniques such as TUNEL (terminal deoxynucleotidyl transferase-mediated nick end labelling) staining and caspase-3 assay. The effect of monensin liposomes on doxorubicin accumulation in MCF-7/dox cells was monitored by fluorescent microscopy. Finally, the expression of MDR genes (MDR1 and MRP1) in MCF-7/dox cells following the exposure to doxorubicin alone and in combination with monensin liposomes was evaluated by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Our results indicated that monensin liposomes overcame drug resistance in MCF-7/dox cells to doxorubicin, etoposide and paclitaxel by 16.5-, 5.6- and 2.8-times, respectively. The combination of doxorubicin (2.5 microg mL(-1)) with monensin liposomes (20 x 10(-8)M) induced apoptosis in approximately 40% cells, whereas doxorubicin (2.5 microg mL(-1)) or monensin liposomes (20 x 10(-8)M) alone produced minimal apoptosis (<10%) in MCF-7/dox cells. Fluorescent microscopy revealed that monensin liposomes increased the accumulation of doxorubicin in MCF-7/dox cells. RT-PCR studies demonstrated that the expression of MDR1 and MRP1 was increased by 33 and 57%, respectively, in MCF-7/dox cells following treatment with doxorubicin (2.5 microg mL(-1)) for 72 h as compared with control MCF-7/dox cells. Furthermore, the levels of MDR1 and MRP1 in MCF-7/dox cells exposed to both doxorubicin and monensin liposomes showed a modest decrease as compared with MCF-7/dox cells treated with doxorubicin alone. In conclusion, the delivery of monensin via liposomes provided an opportunity to overcome drug resistance.

Authors+Show Affiliations

College of Pharmacy and Pharmaceutical Sciences, Florida A&M University,Tallahassee, FL 32307, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

15233869

Citation

Shaik, Madhu Sudhan, et al. "Effects of Monensin Liposomes On the Cytotoxicity, Apoptosis and Expression of Multidrug Resistance Genes in Doxorubicin-resistant Human Breast Tumour (MCF-7/dox) Cell-line." The Journal of Pharmacy and Pharmacology, vol. 56, no. 7, 2004, pp. 899-907.
Shaik MS, Chatterjee A, Singh M. Effects of monensin liposomes on the cytotoxicity, apoptosis and expression of multidrug resistance genes in doxorubicin-resistant human breast tumour (MCF-7/dox) cell-line. J Pharm Pharmacol. 2004;56(7):899-907.
Shaik, M. S., Chatterjee, A., & Singh, M. (2004). Effects of monensin liposomes on the cytotoxicity, apoptosis and expression of multidrug resistance genes in doxorubicin-resistant human breast tumour (MCF-7/dox) cell-line. The Journal of Pharmacy and Pharmacology, 56(7), 899-907.
Shaik MS, Chatterjee A, Singh M. Effects of Monensin Liposomes On the Cytotoxicity, Apoptosis and Expression of Multidrug Resistance Genes in Doxorubicin-resistant Human Breast Tumour (MCF-7/dox) Cell-line. J Pharm Pharmacol. 2004;56(7):899-907. PubMed PMID: 15233869.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of monensin liposomes on the cytotoxicity, apoptosis and expression of multidrug resistance genes in doxorubicin-resistant human breast tumour (MCF-7/dox) cell-line. AU - Shaik,Madhu Sudhan, AU - Chatterjee,Abhijit, AU - Singh,Mandip, PY - 2004/7/6/pubmed PY - 2004/11/4/medline PY - 2004/7/6/entrez SP - 899 EP - 907 JF - The Journal of pharmacy and pharmacology JO - J Pharm Pharmacol VL - 56 IS - 7 N2 - We have evaluated the effects of monensin liposomes on drug resistance reversal, induction of apoptosis and expression of multidrug resistance (MDR) genes in a doxorubicin-resistant human breast tumour (MCF-7/dox) cell line. Monensin liposomes were prepared by the pH-gradient method. MCF-7/dox cells were treated with various anticancer drugs (doxorubicin, paclitaxel and etoposide) alone and in combination with monensin liposomes. The cytotoxicity was assessed using the crystal violet dye uptake method. The induction of apoptosis in MCF-7/dox cells was assessed by established techniques such as TUNEL (terminal deoxynucleotidyl transferase-mediated nick end labelling) staining and caspase-3 assay. The effect of monensin liposomes on doxorubicin accumulation in MCF-7/dox cells was monitored by fluorescent microscopy. Finally, the expression of MDR genes (MDR1 and MRP1) in MCF-7/dox cells following the exposure to doxorubicin alone and in combination with monensin liposomes was evaluated by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Our results indicated that monensin liposomes overcame drug resistance in MCF-7/dox cells to doxorubicin, etoposide and paclitaxel by 16.5-, 5.6- and 2.8-times, respectively. The combination of doxorubicin (2.5 microg mL(-1)) with monensin liposomes (20 x 10(-8)M) induced apoptosis in approximately 40% cells, whereas doxorubicin (2.5 microg mL(-1)) or monensin liposomes (20 x 10(-8)M) alone produced minimal apoptosis (<10%) in MCF-7/dox cells. Fluorescent microscopy revealed that monensin liposomes increased the accumulation of doxorubicin in MCF-7/dox cells. RT-PCR studies demonstrated that the expression of MDR1 and MRP1 was increased by 33 and 57%, respectively, in MCF-7/dox cells following treatment with doxorubicin (2.5 microg mL(-1)) for 72 h as compared with control MCF-7/dox cells. Furthermore, the levels of MDR1 and MRP1 in MCF-7/dox cells exposed to both doxorubicin and monensin liposomes showed a modest decrease as compared with MCF-7/dox cells treated with doxorubicin alone. In conclusion, the delivery of monensin via liposomes provided an opportunity to overcome drug resistance. SN - 0022-3573 UR - https://www.unboundmedicine.com/medline/citation/15233869/Effects_of_monensin_liposomes_on_the_cytotoxicity_apoptosis_and_expression_of_multidrug_resistance_genes_in_doxorubicin_resistant_human_breast_tumour__MCF_7/dox__cell_line_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0022-3573&amp;date=2004&amp;volume=56&amp;issue=7&amp;spage=899 DB - PRIME DP - Unbound Medicine ER -