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Inhibit multidrug resistance and induce apoptosis by using glycocholic acid and epirubicin.
Eur J Pharm Sci. 2008 Sep 02; 35(1-2):52-67.EJ

Abstract

Cancer-cell resistance to chemotherapy limits the efficacy of cancer treatment. The primary mechanisms of multidrug resistance (MDR) are "pump" and "non-pump" resistance. We evaluated the effects and mechanisms of glycocholic acid (GC), a bile acid, on inhibiting pump and non-pump resistance, and increasing the chemosensitivity of epirubicin in human colon adenocarcinoma Caco-2 cells and rat intestine. GC increased the cytotoxicity of epirubicin, significantly increased the intracellular accumulation of epirubicin in Caco-2 cells and the absorption of epirubicin in rat small intestine, and intensified epirubicin-induced apoptosis. GC and epirubicin significantly reduced mRNA expression levels of human intestinal MDR1, MDR-associated protein (MRP)1, and MRP2; downregulated the MDR1 promoter region; suppressed the mRNA expression of Bcl-2; induced the mRNA expression of Bax; and significantly increased the Bax-to-Bcl-2 ratio and the mRNA levels of p53, caspase-9 and -3. This suggests that GC- and epirubicin-induced apoptosis was mediated through the mitochondrial pathway. We conclude that simultaneous suppression of pump and non-pump resistance dramatically increased the chemosensitivity of epirubicin. A combination of anticancer drugs with GC can control MDR via a mechanism that involves modulating P-gp and MRPs as well as regulating apoptosis-related pathways.

Authors+Show Affiliations

Department of Biological Sciences and Technology, National University of Tainan, Tainan City 700, Taiwan. yulilo@mail.nutn.edu.twNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18606222

Citation

Lo, Y L., et al. "Inhibit Multidrug Resistance and Induce Apoptosis By Using Glycocholic Acid and Epirubicin." European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, vol. 35, no. 1-2, 2008, pp. 52-67.
Lo YL, Ho CT, Tsai FL. Inhibit multidrug resistance and induce apoptosis by using glycocholic acid and epirubicin. Eur J Pharm Sci. 2008;35(1-2):52-67.
Lo, Y. L., Ho, C. T., & Tsai, F. L. (2008). Inhibit multidrug resistance and induce apoptosis by using glycocholic acid and epirubicin. European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, 35(1-2), 52-67. https://doi.org/10.1016/j.ejps.2008.06.003
Lo YL, Ho CT, Tsai FL. Inhibit Multidrug Resistance and Induce Apoptosis By Using Glycocholic Acid and Epirubicin. Eur J Pharm Sci. 2008 Sep 2;35(1-2):52-67. PubMed PMID: 18606222.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibit multidrug resistance and induce apoptosis by using glycocholic acid and epirubicin. AU - Lo,Y L, AU - Ho,C T, AU - Tsai,F L, Y1 - 2008/06/20/ PY - 2008/03/04/received PY - 2008/05/26/revised PY - 2008/06/05/accepted PY - 2008/7/9/pubmed PY - 2008/11/1/medline PY - 2008/7/9/entrez SP - 52 EP - 67 JF - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JO - Eur J Pharm Sci VL - 35 IS - 1-2 N2 - Cancer-cell resistance to chemotherapy limits the efficacy of cancer treatment. The primary mechanisms of multidrug resistance (MDR) are "pump" and "non-pump" resistance. We evaluated the effects and mechanisms of glycocholic acid (GC), a bile acid, on inhibiting pump and non-pump resistance, and increasing the chemosensitivity of epirubicin in human colon adenocarcinoma Caco-2 cells and rat intestine. GC increased the cytotoxicity of epirubicin, significantly increased the intracellular accumulation of epirubicin in Caco-2 cells and the absorption of epirubicin in rat small intestine, and intensified epirubicin-induced apoptosis. GC and epirubicin significantly reduced mRNA expression levels of human intestinal MDR1, MDR-associated protein (MRP)1, and MRP2; downregulated the MDR1 promoter region; suppressed the mRNA expression of Bcl-2; induced the mRNA expression of Bax; and significantly increased the Bax-to-Bcl-2 ratio and the mRNA levels of p53, caspase-9 and -3. This suggests that GC- and epirubicin-induced apoptosis was mediated through the mitochondrial pathway. We conclude that simultaneous suppression of pump and non-pump resistance dramatically increased the chemosensitivity of epirubicin. A combination of anticancer drugs with GC can control MDR via a mechanism that involves modulating P-gp and MRPs as well as regulating apoptosis-related pathways. SN - 0928-0987 UR - https://www.unboundmedicine.com/medline/citation/18606222/Inhibit_multidrug_resistance_and_induce_apoptosis_by_using_glycocholic_acid_and_epirubicin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0928-0987(08)00292-3 DB - PRIME DP - Unbound Medicine ER -