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Published on: September 5, 2019
Microarray-based mRNA expression profiling of leukemia cells treated with the flavonoid, casticin
Chiara Righeschi1, Tolga Eichhorn, Anastasia Karioti
1Department of Pharmaceutical Sciences, University of Florence, Florence, Italy.
Abstract:
Natural polyphenols play an important role in tumor inhibition. We used a doxorubicin-sensitive acute T-lymphoblastic leukemia cell line (CCRF-CEM) and its multidrug-resistant subline (CEM/ADR5000) to evaluate the activity of 15 plant polyphenols isolated in our laboratory (hypericin and pseudohypericin, verbascoside, ellagic acid, casticin, kaempferol-3-O-(2'',6''-di-E-p-coumaroyl)-glucopyranoside, kaempferol-3-O-(3,4-diacetyl-2,6-di-E-p-coumaroyl) -glucopyranoside, tiliroside, salvianolic acid B, oleuropein, rosmarinic acid, bergenin) or of others from commercial sources (curcumin, epigallocatechin-3-gallate, silymarin). Casticin was the most potent compound (IC50 values of 0.28 ± 0.02 μM in CCRF-CEM and 0.44 ± 0.17 μM in CEM/ADR5000 cells. The IC50 values of the other compounds tested ranged from 1.52 μM to 164.1 μM. A microarray-based mRNA expression profiling of CCRF-CEM cells treated with casticin was performed in order to identify genes with altered expression following casticin treatment. Networks related to NF-κB, p38MAPK, histones H3 and H4, and follicle stimulating hormone were identified.
Insights
Casticin, a natural polyphenol, demonstrated potent anti-cancer activity against acute T-lymphoblastic leukemia cells, including drug-resistant lines. Further research identified key cellular pathways affected by casticin.
Area of Science:
- Phytochemistry
- Cancer Biology
- Molecular Pharmacology
Background:
- Natural polyphenols are recognized for their potential anti-tumor properties.
- Acute T-lymphoblastic leukemia (T-ALL) poses a significant therapeutic challenge, particularly with the emergence of multidrug resistance.
- Evaluating novel compounds for efficacy against resistant cancer cell lines is crucial for developing new treatments.
Purpose of the Study:
- To assess the anti-leukemic activity of 15 plant-derived polyphenols against a doxorubicin-sensitive and a multidrug-resistant T-ALL cell line.
- To identify the most potent polyphenol compound for further investigation.
- To explore the molecular mechanisms underlying the action of the most effective compound.
Main Methods:
- Cultured doxorubicin-sensitive (CCRF-CEM) and multidrug-resistant (CEM/ADR5000) T-ALL cell lines.
- Assessed the cytotoxic effects of 15 plant polyphenols using IC50 value determination.
- Conducted microarray-based mRNA expression profiling on casticin-treated CCRF-CEM cells.
Main Results:
- Casticin exhibited the highest potency, with low IC50 values in both sensitive (0.28 ± 0.02 μM) and resistant (0.44 ± 0.17 μM) T-ALL cells.
- Other tested polyphenols showed varying degrees of activity, with IC50 values ranging from 1.52 μM to 164.1 μM.
- Casticin treatment altered gene expression in CCRF-CEM cells, implicating pathways such as NF-κB, p38MAPK, and those involving histones and follicle-stimulating hormone.
Conclusions:
- Casticin is a highly potent natural polyphenol with significant anti-leukemic activity against both drug-sensitive and drug-resistant T-ALL.
- The anti-cancer effects of casticin are associated with the modulation of critical cellular signaling pathways.
- Casticin represents a promising candidate for further development as a therapeutic agent for T-ALL.
