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

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

  • Molecules. 2016 Jul 30;21(8):995. doi: 10.3390/molecules21080995.
Aleksandra Mędra 1,  Magdalena Witkowska 2,  Agata Majchrzak 3 4,  Barbara Cebula-Obrzut 5,  Michael Y Bonner 6,  Tadeusz Robak 7,  Jack L Arbiser 8 9,  Piotr Smolewski 10
Affiliations

Affiliations

  • 1 Department of Experimental Hematology of Medical University of Lodz, Ciołkowskiego 2 Street, Lodz 93-510, Poland. [email protected].
  • 2 Department of Experimental Hematology of Medical University of Lodz, Ciołkowskiego 2 Street, Lodz 93-510, Poland. [email protected].
  • 3 Department of Experimental Hematology of Medical University of Lodz, Ciołkowskiego 2 Street, Lodz 93-510, Poland. [email protected].
  • 4 Department of Hematology of Medical University of Lodz, Ciołkowskiego 2 Street, Lodz 93-510, Poland. [email protected].
  • 5 Department of Experimental Hematology of Medical University of Lodz, Ciołkowskiego 2 Street, Lodz 93-510, Poland. [email protected].
  • 6 Winship Cancer Institute, Emory University School of Medicine, 101 Woodruff Cir, Atlanta, GA 30322, USA. [email protected].
  • 7 Department of Hematology of Medical University of Lodz, Ciołkowskiego 2 Street, Lodz 93-510, Poland. [email protected].
  • 8 Winship Cancer Institute, Emory University School of Medicine, 101 Woodruff Cir, Atlanta, GA 30322, USA. [email protected].
  • 9 Atlanta Veterans Administration Hospital, 1670 Clairmont Road, Decatur, GA 30033, USA. [email protected].
  • 10 Department of Experimental Hematology of Medical University of Lodz, Ciołkowskiego 2 Street, Lodz 93-510, Poland. [email protected].
PMID: 27483232 DOI: 10.3390/molecules21080995
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.

Keywords

ALL; BL; CLL; DLBCL; MM; honokiol analogues.

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