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Molecules 2016, 21(8), 995; doi:10.3390/molecules21080995

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

1
Department of Experimental Hematology of Medical University of Lodz, Ciołkowskiego 2 Street, Lodz 93-510, Poland
2
Department of Hematology of Medical University of Lodz, Ciołkowskiego 2 Street, Lodz 93-510, Poland
3
Winship Cancer Institute, Emory University School of Medicine, 101 Woodruff Cir, Atlanta, GA 30322, USA
4
Atlanta Veterans Administration Hospital, 1670 Clairmont Road, Decatur, GA 30033, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Diego Muñoz-Torrero
Received: 6 June 2016 / Revised: 15 July 2016 / Accepted: 18 July 2016 / Published: 30 July 2016
(This article belongs to the Section Medicinal Chemistry)
View Full-Text   |   Download PDF [1629 KB, uploaded 30 July 2016]   |  

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. View Full-Text
Keywords: honokiol analogues; CLL; ALL; BL; DLBCL; MM honokiol analogues; CLL; ALL; BL; DLBCL; MM
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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. (CC BY 4.0).

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MDPI and ACS Style

Mędra, A.; Witkowska, M.; Majchrzak, A.; Cebula-Obrzut, B.; Bonner, M.Y.; Robak, T.; Arbiser, J.L.; Smolewski, P. Pro-Apoptotic Activity of New Honokiol/Triphenylmethane Analogues in B-Cell Lymphoid Malignancies. Molecules 2016, 21, 995.

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