A Novel Drug Modulator Diarylheptanoid (<i>t</i><i>rans</i>-1,7-Diphenyl-5-hydroxy-1-heptene) from <i>Curcuma comosa</i> Rhizomes for P-glycoprotein Function and Apoptosis Induction in K652/ADR Leukemic Cells
<i>Curcuma comosa</i> has been used in traditional Thai medicine to treat menstrual cycle-related symptoms in women. This study aims to evaluate the diarylheptanoid drug modulator, <i>t</i><i>rans</i>-1,7-diphenyl-5-hydroxy-1-heptene (DHH), in drug-resistant K562/...
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| Format: | Article |
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/16/8989 |
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| author | Natsima Viriyaadhammaa Suwit Duangmano Aroonchai Saiai Montree Tungjai Pornngarm Dejkriengkraikul Singkome Tima Sawitree Chiampanichayakul Jeffrey Krise Songyot Anuchapreeda |
| author_facet | Natsima Viriyaadhammaa Suwit Duangmano Aroonchai Saiai Montree Tungjai Pornngarm Dejkriengkraikul Singkome Tima Sawitree Chiampanichayakul Jeffrey Krise Songyot Anuchapreeda |
| author_sort | Natsima Viriyaadhammaa |
| collection | DOAJ |
| description | <i>Curcuma comosa</i> has been used in traditional Thai medicine to treat menstrual cycle-related symptoms in women. This study aims to evaluate the diarylheptanoid drug modulator, <i>t</i><i>rans</i>-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 IC<sub>50</sub> 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. |
| first_indexed | 2024-03-09T04:20:51Z |
| format | Article |
| id | doaj.art-53c3bec498d7454cb303ab41151e3ee1 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T04:20:51Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-53c3bec498d7454cb303ab41151e3ee12023-12-03T13:47:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316898910.3390/ijms23168989A Novel Drug Modulator Diarylheptanoid (<i>t</i><i>rans</i>-1,7-Diphenyl-5-hydroxy-1-heptene) from <i>Curcuma comosa</i> Rhizomes for P-glycoprotein Function and Apoptosis Induction in K652/ADR Leukemic CellsNatsima Viriyaadhammaa0Suwit Duangmano1Aroonchai Saiai2Montree Tungjai3Pornngarm Dejkriengkraikul4Singkome Tima5Sawitree Chiampanichayakul6Jeffrey Krise7Songyot Anuchapreeda8Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200, ThailandCancer Research Unit of Associated Medical Sciences (AMS CRU), Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandPharmaceutical Chemistry, School of Pharmacy, University of Kansas, Lawrence, KS 66045, USADepartment of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand<i>Curcuma comosa</i> has been used in traditional Thai medicine to treat menstrual cycle-related symptoms in women. This study aims to evaluate the diarylheptanoid drug modulator, <i>t</i><i>rans</i>-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 IC<sub>50</sub> 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.https://www.mdpi.com/1422-0067/23/16/8989<i>Curcuma comosa</i>diarylheptanoid<i>trans</i>-1,7-diphenyl-5-hydroxy-1-heptenemultidrug resistanceMDR modulatorantileukemia |
| spellingShingle | Natsima Viriyaadhammaa Suwit Duangmano Aroonchai Saiai Montree Tungjai Pornngarm Dejkriengkraikul Singkome Tima Sawitree Chiampanichayakul Jeffrey Krise Songyot Anuchapreeda A Novel Drug Modulator Diarylheptanoid (<i>t</i><i>rans</i>-1,7-Diphenyl-5-hydroxy-1-heptene) from <i>Curcuma comosa</i> Rhizomes for P-glycoprotein Function and Apoptosis Induction in K652/ADR Leukemic Cells International Journal of Molecular Sciences <i>Curcuma comosa</i> diarylheptanoid <i>trans</i>-1,7-diphenyl-5-hydroxy-1-heptene multidrug resistance MDR modulator antileukemia |
| title | A Novel Drug Modulator Diarylheptanoid (<i>t</i><i>rans</i>-1,7-Diphenyl-5-hydroxy-1-heptene) from <i>Curcuma comosa</i> Rhizomes for P-glycoprotein Function and Apoptosis Induction in K652/ADR Leukemic Cells |
| title_full | A Novel Drug Modulator Diarylheptanoid (<i>t</i><i>rans</i>-1,7-Diphenyl-5-hydroxy-1-heptene) from <i>Curcuma comosa</i> Rhizomes for P-glycoprotein Function and Apoptosis Induction in K652/ADR Leukemic Cells |
| title_fullStr | A Novel Drug Modulator Diarylheptanoid (<i>t</i><i>rans</i>-1,7-Diphenyl-5-hydroxy-1-heptene) from <i>Curcuma comosa</i> Rhizomes for P-glycoprotein Function and Apoptosis Induction in K652/ADR Leukemic Cells |
| title_full_unstemmed | A Novel Drug Modulator Diarylheptanoid (<i>t</i><i>rans</i>-1,7-Diphenyl-5-hydroxy-1-heptene) from <i>Curcuma comosa</i> Rhizomes for P-glycoprotein Function and Apoptosis Induction in K652/ADR Leukemic Cells |
| title_short | A Novel Drug Modulator Diarylheptanoid (<i>t</i><i>rans</i>-1,7-Diphenyl-5-hydroxy-1-heptene) from <i>Curcuma comosa</i> Rhizomes for P-glycoprotein Function and Apoptosis Induction in K652/ADR Leukemic Cells |
| title_sort | novel drug modulator diarylheptanoid i t i i rans i 1 7 diphenyl 5 hydroxy 1 heptene from i curcuma comosa i rhizomes for p glycoprotein function and apoptosis induction in k652 adr leukemic cells |
| topic | <i>Curcuma comosa</i> diarylheptanoid <i>trans</i>-1,7-diphenyl-5-hydroxy-1-heptene multidrug resistance MDR modulator antileukemia |
| url | https://www.mdpi.com/1422-0067/23/16/8989 |
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