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A Novel Drug Modulator Diarylheptanoid (trans-1,7-Diphenyl-5-hydroxy-1-heptene) from Curcuma comosa Rhizomes for P-glycoprotein Function and Apoptosis Induction in K652/ADR Leukemic Cells

Viriyaadhammaa, Natsima
; 
Duangmano, Suwit
; 
Saiai, Aroonchai
; 
Tungjai, Montree
; 
Dejkriengkraikul, Pornngarm
; 
Tima, Singkome
; 
Chiampanichayakul, Sawitree
; 
Krise, Jeffrey
; 
Anuchapreeda, Songyot
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Abstract
Curcuma comosa has been used in traditional Thai medicine to treat menstrual cycle-related symptoms in women. This study aims to evaluate the diarylheptanoid drug modulator, trans-1,7-diphenyl-5-hydroxy-1-heptene (DHH), in drug-resistant K562/ADR human leukemic cells. This compound was studied due to its effects on cell cytotoxicity, multidrug resistance (MDR) phenotype, P-glycoprotein (P-gp) expression, and P-gp function. We show that DHH itself is cytotoxic towards K562/ADR cells. However, DHH did not impact P-gp expression. The impact of DHH on the MDR phenotype in the K562/ADR cells was determined by co-treatment of cells with doxorubicin (Dox) and DHH using an MTT assay. The results showed that the DHH changed the MDR phenotype in the K562/ADR cells by decreasing the IC50 of Dox from 51.6 to 18.2 µM. Treating the cells with a nontoxic dose of DHH increased their sensitivity to Dox in P-gp expressing drug-resistant cells. The kinetics of P-gp mediated efflux of pirarubicin (THP) was used to monitor the P-gp function. DHH was shown to suppress THP efflux and resulted in enhanced apoptosis in the K562/ADR cells. These results demonstrate that DHH is a novel drug modulator of P-gp function and induces drug accumulation in the Dox-resistant K562 leukemic cell line.
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Date
2022-08-12
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MDPI
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Pharmaceutical Chemistry Scholarly Works
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Keywords
Curcuma comosa, Diarylheptanoid, trans-1,7-diphenyl-5-hydroxy-1-heptene, Multidrug resistance, MDR modulator, Antileukemia
Citation
Viriyaadhammaa, N.; Duangmano, S.; Saiai, A.; Tungjai, M.; Dejkriengkraikul, P.; Tima, S.; Chiampanichayakul, S.; Krise, J.; Anuchapreeda, S. A Novel Drug Modulator Diarylheptanoid (trans-1,7-Diphenyl-5-hydroxy-1-heptene) from Curcuma comosa Rhizomes for P-glycoprotein Function and Apoptosis Induction in K652/ADR Leukemic Cells. Int. J. Mol. Sci. 2022, 23, 8989. https://doi.org/10.3390/ijms23168989
URI
https://hdl.handle.net/1808/33613
DOI
10.3390/ijms23168989
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