Active Compounds from Curcuma Comosa Roxb. for Multidrug Resistance Reversal and Nucleophosmin Inhibitory Abilities in Drug Resistance Leukemic Cells

Abstract

This study aimed to explore the potential of main compounds from Curcuma comosa Roxb. in leukemia treatment. The Diarylheptanoid 7-(3,4-dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene (compound 1 or DDHPH) was obtained after purification from ethyl acetate (F-EtOAc) fractional extract, while diarylheptanoid trans-1,7-diphenyl-5-hydroxy-1-heptene (compound 2 or DHH) was obtained after purification from hexane (F-Hex) fractional extract. Both compounds 1 and 2 exhibited strong cytotoxicity against various cancer cell lines, while remaining nontoxicity toward normal white blood cells. Additionally, compound 1 demonstrated notable antioxidant and anti-inflammatory properties.

This study focused on proteins associated with cell proliferation and cell death. WT1 protein, a marker for leukemic cell proliferation, was significantly decreased after F-EtOAC and compound 1 treatments in a time- and dose-dependent manner. Moreover, compound 1 was found to induce NPM localization, resulting in the upregulation of p53 leading to cell cycle arrest and apoptosis. On the other hand, compound 2 demonstrated a drug modulator property, enhancing the efficacy of chemotherapeutic agents in drug-resistant cells.

In conclusion, this study successfully purified the main active compounds from C. comosa Roxb., including compound 1 and compound 2. These two compounds could reduce cancer cell survival and safe for normal cells, indicating their potential as models for drug development.