Trifolium Repens Blocks Proliferation in Chronic Myelogenous Leukemia via the BCR-ABL/STAT5 Pathway
by
Federica Sarno 1, Giacomo Pepe 2, Pasquale Termolino 3, Vincenzo Carafa 1, Crescenzo Massaro 1, Fabrizio Merciai 2,4, Pietro Campiglia 2,5, Angela Nebbioso 1,* and 
Lucia Altucci 1,*
Federica Sarno 1, Giacomo Pepe 2, Pasquale Termolino 3, Vincenzo Carafa 1, Crescenzo Massaro 1, Fabrizio Merciai 2,4, Pietro Campiglia 2,5, Angela Nebbioso 1,* and Lucia Altucci 1,*
1
Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
2
Department of Pharmacy, School of Pharmacy, University of Salerno, 84084 Fisciano, Italy
3
Institute of Biosciences and Bioresources (IBBR), National Research Council of Italy (CNR), 80055 Portici, Italy
4
PhD Program in Drug Discovery and Development, University of Salerno, 84084 Fisciano, Italy
5
European Biomedical Research Institute of Salerno, 84125 Salerno, Italy
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(2), 379; https://doi.org/10.3390/cells9020379
Received: 23 December 2019 / Revised: 27 January 2020 / Accepted: 3 February 2020 / Published: 6 February 2020
(This article belongs to the Special Issue Role of the G Protein-Coupled Receptors in Cancer and Stromal Cells: From Functions to Novel Therapeutic Perspectives)
Some species of clover are reported to have beneficial effects in human diseases. However, little is known about the activity of the forage plant Trifolium repens, or white clover, which has been recently found to exert a hepatoprotective action. Scientific interest is increasingly focused on identifying new drugs, especially natural products and their derivatives, to treat human diseases including cancer. We analyzed the anticancer effects of T. repens in several cancer cell lines. The phytochemical components of T. repens were first extracted in a methanol solution and then separated into four fractions by ultra-high-performance liquid chromatography. The effects of the total extract and each fraction on cancer cell proliferation were analyzed by MTT assay and Western blotting. T. repens and, more robustly, its isoflavonoid-rich fraction showed high cytotoxic effects in chronic myelogenous leukemia (CML) K562 cells, with IC50 values of 1.67 and 0.092 mg/mL, respectively. The block of cell growth was associated with a total inhibition of BCR-ABL/STAT5 and activation of the p38 signaling pathways. In contrast, these strongly cytotoxic effects did not occur in normal cells. Our findings suggest that the development of novel compounds derived from phytochemical molecules contained in Trifolium might lead to the identification of new therapeutic agents active against CML.
Keywords:
Trifolium repens; isoflavonoids; polyphenols; cancer; chronic myelogenous leukemia; K562 cells; BCR-ABL/STAT5
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
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MDPI and ACS Style
Sarno, F.; Pepe, G.; Termolino, P.; Carafa, V.; Massaro, C.; Merciai, F.; Campiglia, P.; Nebbioso, A.; Altucci, L. Trifolium Repens Blocks Proliferation in Chronic Myelogenous Leukemia via the BCR-ABL/STAT5 Pathway. Cells 2020, 9, 379.
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