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

• Type of Material: Article
• Authors: Aleksandra Medra, Medical University of Lodz; Magdalena Witkowska, Medical University of Lodz; Agata Majchrzak, Medical University of Lodz; Barbara Cebula-Obrzut, Medical University of Lodz; Michael Y. Bonner, Emory University; Tadeusz Robak, Medical University of Lodz; Jack Arbiser, Emory University; Piotr Smolewski, Medical University of Lodz
• Language: English
• Date: 2016-08-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2016 by the authors; licensee MDPI, Basel, Switzerland.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/molecules21080995
• Title of Journal or Parent Work: Molecules
• ISSN: 1420-3049
• Volume: 21
• Issue: 8
• Start Page: 995
• End Page: 995
• Grant/Funding Information: The study was supported in part by grant funding from The Medical University of Lodz, Poland: Grants No. 502-03/8-093-01/502-64-032 and No. 503/8-093-01/503-01; the Margolis Family Foundation; the Rabinowitch-Davis Foundation; the Minsk Foundation; and NIH RO1AR47901.
• Keywords: IN-VITRO; MM; Physical Sciences; Science & Technology; CHRONIC LYMPHOCYTIC-LEUKEMIA; CYTOCHROME-C; honokiol analogues; CLL; MAGNOLOL; CH27 CELLS; HONOKIOL INDUCES APOPTOSIS; Biochemistry & Molecular Biology; Chemistry; BL; CANCER; Chemistry, Multidisciplinary; DLBCL; NATURAL-PRODUCT; ALL; PHENOLIC CONSTITUENTS; ACTIVATION; Life Sciences & Biomedicine
• Research Categories: Biology, Molecular; Chemistry, General; Health Sciences, Oncology

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.