Chemosensitizing effects of synthetic curcumin analogs on human multi-drug resistance leukemic cells
© 2015 Elsevier Ireland Ltd. All rights reserved. Curcumin analogs were synthesized and their multi-drug resistance (MDR) reversing properties were determined in human MDR leukemic (K562/Adr) cells. Four analogs, 1,7-bis-(3,4-dimethoxy-phenyl)-hepta-1,6-diene-3,5-dione (1J), 2,6-bis-(4-hydroxy-3-met...
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th-cmuir.6653943832-562832018-09-05T03:12:27Z Chemosensitizing effects of synthetic curcumin analogs on human multi-drug resistance leukemic cells Sariya Mapoung Pornsiri Pitchakarn Supachai Yodkeeree Chitchamai Ovatlarnporn Natee Sakorn Pornngarm Limtrakul Pharmacology, Toxicology and Pharmaceutics © 2015 Elsevier Ireland Ltd. All rights reserved. Curcumin analogs were synthesized and their multi-drug resistance (MDR) reversing properties were determined in human MDR leukemic (K562/Adr) cells. Four analogs, 1,7-bis-(3,4-dimethoxy-phenyl)-hepta-1,6-diene-3,5-dione (1J), 2,6-bis-(4-hydroxy-3-methoxy-benzylidene)-cyclohexanone (2A), 2,6-bis-(3,4-dihydroxy-benzylidene)-cyclohexanone (2F) and 2,6-bis-(3,4-dimethoxy-benzylidene)-cyclohexanone (2J) markedly increased the sensitivity of K562/Adr cells to paclitaxel (PTX) for 8-, 2-, 8- and 16- folds, respectively and vinblastine (Vin) for 5-, 3-, 12- and 30- folds, respectively. The accumulation of P-gp substrates, Calcein-AM, Rhodamine 123 and Doxorubicin, was significantly increased by 1J (up to 6-, 11- and 22- folds, respectively) and 2J (up to 7-, 12- and 17- folds, respectively). Besides 2A, 2F and 2J dramatically decreased P-gp expression in K562/Adr cells. These results could be summarized in the following way. Analog 1J inhibited only P-gp function, while 2A and 2F inhibited only P-gp expression. Interestingly, 2J exerts inhibition of both P-gp function and expression. The combination index (CI) of combination between 2J and PTX (0.09) or Vin (0.06) in K562/Adr cells indicated strong synergistic effects, which likely due to its MDR reversing activity. Moreover, these analogs showed less cytotoxicity to peripheral mononuclear cells (human) and red blood cells (human and rat) suggesting the safety of analogs for further animal and clinical studies. 2018-09-05T03:12:27Z 2018-09-05T03:12:27Z 2016-01-25 Journal 18727786 00092797 2-s2.0-84961303608 10.1016/j.cbi.2015.12.001 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84961303608&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/56283 |
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Pharmacology, Toxicology and Pharmaceutics Sariya Mapoung Pornsiri Pitchakarn Supachai Yodkeeree Chitchamai Ovatlarnporn Natee Sakorn Pornngarm Limtrakul Chemosensitizing effects of synthetic curcumin analogs on human multi-drug resistance leukemic cells |
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© 2015 Elsevier Ireland Ltd. All rights reserved. Curcumin analogs were synthesized and their multi-drug resistance (MDR) reversing properties were determined in human MDR leukemic (K562/Adr) cells. Four analogs, 1,7-bis-(3,4-dimethoxy-phenyl)-hepta-1,6-diene-3,5-dione (1J), 2,6-bis-(4-hydroxy-3-methoxy-benzylidene)-cyclohexanone (2A), 2,6-bis-(3,4-dihydroxy-benzylidene)-cyclohexanone (2F) and 2,6-bis-(3,4-dimethoxy-benzylidene)-cyclohexanone (2J) markedly increased the sensitivity of K562/Adr cells to paclitaxel (PTX) for 8-, 2-, 8- and 16- folds, respectively and vinblastine (Vin) for 5-, 3-, 12- and 30- folds, respectively. The accumulation of P-gp substrates, Calcein-AM, Rhodamine 123 and Doxorubicin, was significantly increased by 1J (up to 6-, 11- and 22- folds, respectively) and 2J (up to 7-, 12- and 17- folds, respectively). Besides 2A, 2F and 2J dramatically decreased P-gp expression in K562/Adr cells. These results could be summarized in the following way. Analog 1J inhibited only P-gp function, while 2A and 2F inhibited only P-gp expression. Interestingly, 2J exerts inhibition of both P-gp function and expression. The combination index (CI) of combination between 2J and PTX (0.09) or Vin (0.06) in K562/Adr cells indicated strong synergistic effects, which likely due to its MDR reversing activity. Moreover, these analogs showed less cytotoxicity to peripheral mononuclear cells (human) and red blood cells (human and rat) suggesting the safety of analogs for further animal and clinical studies. |
format |
Journal |
author |
Sariya Mapoung Pornsiri Pitchakarn Supachai Yodkeeree Chitchamai Ovatlarnporn Natee Sakorn Pornngarm Limtrakul |
author_facet |
Sariya Mapoung Pornsiri Pitchakarn Supachai Yodkeeree Chitchamai Ovatlarnporn Natee Sakorn Pornngarm Limtrakul |
author_sort |
Sariya Mapoung |
title |
Chemosensitizing effects of synthetic curcumin analogs on human multi-drug resistance leukemic cells |
title_short |
Chemosensitizing effects of synthetic curcumin analogs on human multi-drug resistance leukemic cells |
title_full |
Chemosensitizing effects of synthetic curcumin analogs on human multi-drug resistance leukemic cells |
title_fullStr |
Chemosensitizing effects of synthetic curcumin analogs on human multi-drug resistance leukemic cells |
title_full_unstemmed |
Chemosensitizing effects of synthetic curcumin analogs on human multi-drug resistance leukemic cells |
title_sort |
chemosensitizing effects of synthetic curcumin analogs on human multi-drug resistance leukemic cells |
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2018 |
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https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84961303608&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/56283 |
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