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

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      ATP Binding Cassette Transporter, Subfamily B, Member 1*/metabolism ; Antineoplastic Agents*/pharmacology ; Curcuma*/chemistry ; Diarylheptanoids*/pharmacology; Apoptosis ; Biphenyl Compounds ; Doxorubicin/pharmacology ; Drug Resistance, Neoplasm ; Humans ; K562 Cells ; Rhizome/metabolism
    • 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, t rans -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 50 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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    • Grant Information:
      RSA6280034 Thailand Research Fund; PHD/0026/2560 Thailand Research Fund
    • Contributed Indexing:
      Keywords: Curcuma comosa; MDR modulator; antileukemia; diarylheptanoid; multidrug resistance; trans-1,7-diphenyl-5-hydroxy-1-heptene
    • Accession Number:
      0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
      0 (Antineoplastic Agents)
      0 (Biphenyl Compounds)
      0 (Diarylheptanoids)
      2L9GJK6MGN (diphenyl)
      80168379AG (Doxorubicin)
    • Publication Date:
      Date Created: 20220826 Date Completed: 20220829 Latest Revision: 20220830
    • Publication Date:
      20240829
    • Accession Number:
      PMC9409401
    • Accession Number:
      10.3390/ijms23168989
    • Accession Number:
      36012254