Virdis Patrizia, Migheli Rossana, Galleri Grazia, Fancello Silvia, Cadoni Maria Piera L, Pintore Giorgio, Petretto Giacomo Luigi, Marchesi Irene, Fiorentino Francesco Paolo, di Francesco Alessandra, Sanges Francesca, Bagella Luigi, Muroni Maria Rosaria, Fozza Claudio, De Miglio Maria Rosaria, Podda Luigi
Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy.
Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy.
Tumour Biol. 2020 Feb;42(2):1010428319901061. doi: 10.1177/1010428319901061.
Burkitt lymphoma is a very aggressive B-cell non-Hodgkin lymphoma. Although remarkable progress has been made in the therapeutic scenario for patients with Burkitt lymphoma, search and development of new effective anticancer agents to improve patient outcome and minimize toxicity has become an urgent issue. In this study, the antitumoral activity of , a traditional herb obtained from plants collected on the Asinara Island, Italy, was evaluated in order to explore potential antineoplastic effects of its metabolites on Burkitt lymphoma. Raji human cell line was treated with increasing extract concentration for cytotoxicity screening and subsequent establishment of cell cycle arrest and apoptosis. Moreover, gene expression profiles were performed to identify molecular mechanisms involved in the anticancer activities of this medical plant. The extract exhibited powerful antiproliferative and cytotoxic activities on Raji cell line, showing a dose- and time-dependent decrease in cell viability, obtained by cell cycle arrest in the G2/M phase and an increase in cell apoptosis. The treatment with caused downregulation of genes involved in cell cycle and proliferation (c-MYC, CCND1) and inhibition of cell apoptosis (BCL2, BCL2L1, BCL11A). The extract causes strong anticancer effects on Burkitt lymphoma cell line. The molecular mechanisms underlying such antineoplastic activity are based on targeting and downregulation of genes involved in cell cycle and apoptosis. Our data suggest that natural metabolites should be further exploited as potential antineoplastic agents against Burkitt lymphoma.
伯基特淋巴瘤是一种侵袭性很强的B细胞非霍奇金淋巴瘤。尽管在伯基特淋巴瘤患者的治疗方面已取得显著进展，但寻找和开发新的有效抗癌药物以改善患者预后并将毒性降至最低已成为一个紧迫问题。在本研究中，对一种从意大利阿西纳拉岛采集的植物中获得的传统草药的抗肿瘤活性进行了评估，以探索其代谢产物对伯基特淋巴瘤的潜在抗肿瘤作用。用递增浓度的该提取物处理拉吉人细胞系以进行细胞毒性筛选，并随后确定细胞周期停滞和凋亡情况。此外，进行基因表达谱分析以确定参与这种药用植物抗癌活性的分子机制。该提取物对拉吉细胞系表现出强大的抗增殖和细胞毒性活性，通过使细胞周期停滞在G2/M期以及增加细胞凋亡，显示出细胞活力呈剂量和时间依赖性下降。该提取物处理导致参与细胞周期和增殖的基因（c-MYC、CCND1）下调以及抑制细胞凋亡的基因（BCL2、BCL2L1、BCL11A）表达降低。该提取物对伯基特淋巴瘤细胞系具有强大的抗癌作用。这种抗肿瘤活性背后的分子机制基于对参与细胞周期和凋亡的基因进行靶向和下调。我们的数据表明，该天然代谢产物应进一步作为针对伯基特淋巴瘤的潜在抗肿瘤药物加以开发利用。
