Bontempo Paola, Mita Luigi, Miceli Marco, Doto Antonella, Nebbioso Angela, De Bellis Floriana, Conte Mariarosaria, Minichiello Annunziata, Manzo Fabio, Carafa Vincenzo, Basile Adriana, Rigano Daniela, Sorbo Sergio, Castaldo Cobianchi Rosa, Schiavone Ettore Mariano, Ferrara Felicetto, De Simone Mariacarla, Vietri MariaTeresa, Cioffi Michele, Sica Vincenzo, Bresciani Francesco, de Lera Angel R, Altucci Lucia, Molinari Anna Maria
Dipartimento di Patologia Generale, Seconda Università degli Studi di Napoli, vico L. De Crecchio 7, 80138 Napoli, Italy.
Int J Biochem Cell Biol. 2007;39(10):1902-14. doi: 10.1016/j.biocel.2007.05.010. Epub 2007 May 25.
Curative properties of some medicinal plants such as the Feijoa sellowiana Bert. (Myrtaceae), have been often claimed, although the corresponding molecular mechanism(s) remain elusive. We report here that the Feijoa acetonic extract exerts anti-cancer activities on solid and hematological cancer cells. Feijoa extract did not show toxic effects on normal myeloid progenitors thus displaying a tumor-selective activity. In the Feijoa acetonic extract, fractionation and subsequent purification and analyses identified Flavone as the active component. Flavone induces apoptosis which is accompanied by caspase activation and p16, p21 and TRAIL over-expression in human myeloid leukemia cells. Use of ex vivo myeloid leukemia patients blasts confirms that both the full acetonic Feijoa extract and its derived Flavone are able to induce apoptosis. In both cell lines and myeloid leukemia patients blasts the apoptotic activity of Feijoa extract and Flavone is accompanied by increase of histone and non-histone acetylation levels and by HDAC inhibition. Our findings show for the first time that the Feijoa apoptotic active principle is the Flavone and that this activity correlates with the induction of HDAC inhibition, supporting the hypothesis of its epigenetic pro-apoptotic regulation in cancer systems.
一些药用植物，如费约果（Feijoa sellowiana Bert.，桃金娘科），其治疗特性常被提及，尽管相应的分子机制仍不清楚。我们在此报告，费约果丙酮提取物对实体瘤和血液系统癌细胞具有抗癌活性。费约果提取物对正常髓系祖细胞未显示出毒性作用，因此表现出肿瘤选择性活性。在费约果丙酮提取物中，通过分级分离、随后的纯化和分析确定黄酮为活性成分。黄酮诱导人髓系白血病细胞凋亡，伴有半胱天冬酶激活以及p16、p21和TRAIL的过表达。使用离体髓系白血病患者的原始细胞证实，完整的费约果丙酮提取物及其衍生的黄酮都能够诱导凋亡。在细胞系和髓系白血病患者的原始细胞中，费约果提取物和黄酮的凋亡活性都伴随着组蛋白和非组蛋白乙酰化水平的增加以及HDAC抑制。我们的研究结果首次表明，费约果的凋亡活性成分是黄酮，并且这种活性与HDAC抑制的诱导相关，支持其在癌症系统中通过表观遗传进行促凋亡调节的假说。
