新厚朴酚/三苯甲烷类似物在B细胞淋巴瘤中的促凋亡活性

Pro-Apoptotic Activity of New Honokiol/Triphenylmethane Analogues in B-Cell Lymphoid Malignancies.

作者信息

Mędra Aleksandra, Witkowska Magdalena, Majchrzak Agata, Cebula-Obrzut Barbara, Bonner Michael Y, Robak Tadeusz, Arbiser Jack L, Smolewski Piotr

机构信息

Department of Experimental Hematology of Medical University of Lodz, Ciołkowskiego 2 Street, Lodz 93-510, Poland.

Department of Hematology of Medical University of Lodz, Ciołkowskiego 2 Street, Lodz 93-510, Poland.

出版信息

Molecules. 2016 Jul 30;21(8):995. doi: 10.3390/molecules21080995.

DOI:10.3390/molecules21080995

PMID:27483232

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6274336/

Abstract

Honokiol and triphenylmethanes are small molecules with anti-tumor properties. Recently, we synthesized new honokiol analogues (HAs) that possess common features of both groups. We assessed the anti-tumor effectiveness of HAs in B-cell leukemia/lymphoma cells, namely in chronic lymphocytic leukemia (CLL) cells ex vivo and in pre-B-cell acute lymphoblastic leukemia (Nalm-6), Burkitt lymphoma (BL; Raji), diffuse large B-cell lymphoma (DLBCL; Toledo) and multiple myeloma (MM; RPMI 8226) cell lines. Four of these compounds appeared to be significantly active against the majority of cells examined, with no significant impact on healthy lymphocytes. These active HAs induced caspase-dependent apoptosis, causing significant deregulation of several apoptosis-regulating proteins. Overall, these compounds downregulated Bcl-2 and XIAP and upregulated Bax, Bak and survivin proteins. In conclusion, some of the HAs are potent tumor-selective inducers of apoptosis in ex vivo CLL and in BL, DLBCL and MM cells in vitro. Further preclinical studies of these agents are recommended.

摘要

厚朴酚和三苯甲烷是具有抗肿瘤特性的小分子。最近，我们合成了具有这两类化合物共同特征的新型厚朴酚类似物（HAs）。我们评估了HAs对B细胞白血病/淋巴瘤细胞的抗肿瘤效果，即在慢性淋巴细胞白血病（CLL）细胞的体外实验以及前B细胞急性淋巴细胞白血病（Nalm-6）、伯基特淋巴瘤（BL；Raji）、弥漫性大B细胞淋巴瘤（DLBCL；Toledo）和多发性骨髓瘤（MM；RPMI 8226）细胞系中的效果。这些化合物中的四种对大多数检测细胞表现出显著活性，对健康淋巴细胞无显著影响。这些活性HAs诱导半胱天冬酶依赖性凋亡，导致几种凋亡调节蛋白的显著失调。总体而言，这些化合物下调了Bcl-2和XIAP，并上调了Bax、Bak和survivin蛋白。总之，一些HAs在体外CLL以及BL、DLBCL和MM细胞中是有效的肿瘤选择性凋亡诱导剂。建议对这些药物进行进一步的临床前研究。