Adorisio Sabrina, Fierabracci Alessandra, Cham Ba Thi, Hoang Vu Dinh, Thuy Linh Nguyen Thi, Nhung Le Thi Hong, Martelli Maria Paola, Ayroldi Emira, Ronchetti Simona, Rosati Lucrezia, Di Giacomo Silvia, Thuy Trinh Thi, Delfino Domenico Vittorio
Section of Pharmacology, Department of Medicine and Surgery, University of Perugia, 06129 Perugia, Italy.
Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
Pharmaceuticals (Basel). 2024 Nov 21;17(12):1561. doi: 10.3390/ph17121561.
The expression of oncogene zinc-finger protein 217 (ZNF217) has been reported to play a central role in cancer development, resistance, and recurrence. Therefore, targeting ZNF217 has been proposed as a possible strategy to fight cancer, and there has been much research on compounds that can target ZNF217. The present work investigates the chemo-preventive properties of cucurbitacin D, a compound with a broad range of anticancer effects, in hematological cancer cells, specifically with regard to its ability to modulate ZNF217 expression. Different cucurbitacins were isolated from the Vietnamese plant . The purified compounds were tested on nucleophosmin-mutated acute myeloid leukemia and other hematological cancer cell lines to assess their effects on the cell cycle, cell viability and apoptosis, and the expression of ZNF217. Cucurbitacin D resulted in a reduction in the number of acute myeloid leukemia cells by inducing an increase in apoptosis and blocking cell cycle progression. It also led to a significant decrease in ZNF217 expression in the nucleophosmin-mutated acute myeloid leukemia cell line but not in the other hematologic cancer cell lines. The reduction in ZNF217 expression contributed significantly to the blocking of cell cycle progression but did not affect apoptosis. The obtained results suggest that cucurbitacin D is a promising molecule for targeting mutated nucleophosmin or its pathway in acute myeloid leukemia cells, although further studies are needed for in-depth investigations into its specific mechanisms.
据报道，癌基因锌指蛋白217（ZNF217）的表达在癌症的发展、耐药性和复发中起着核心作用。因此，靶向ZNF217已被提议作为一种抗癌的可能策略，并且针对能够靶向ZNF217的化合物已经开展了大量研究。目前的研究工作考察了葫芦素D在血液癌细胞中的化学预防特性，葫芦素D是一种具有广泛抗癌作用的化合物，具体考察了其调节ZNF217表达的能力。从越南植物中分离出了不同的葫芦素。对纯化后的化合物在核磷蛋白突变的急性髓系白血病细胞和其他血液癌细胞系上进行测试，以评估它们对细胞周期、细胞活力和凋亡以及ZNF217表达的影响。葫芦素D通过诱导凋亡增加和阻断细胞周期进程，使急性髓系白血病细胞数量减少。它还导致核磷蛋白突变的急性髓系白血病细胞系中ZNF217表达显著降低，但在其他血液癌细胞系中未出现这种情况。ZNF217表达的降低对细胞周期进程的阻断有显著作用，但不影响凋亡。所得结果表明，葫芦素D是一种有前景的分子，可用于靶向急性髓系白血病细胞中突变的核磷蛋白或其信号通路，不过还需要进一步研究以深入探究其具体机制。
