title: Pro-Apoptotic Activity of New Honokiol/Triphenylmethane Analogues in B-Cell Lymphoid Malignancies.
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.
authors.affiliation: Department of Experimental Hematology of Medical University of Lodz, Cio&#322;kowskiego 2 Street, Lodz 93-510, Poland. olajeske@o2.pl.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Mędra
authors.affiliation: Department of Experimental Hematology of Medical University of Lodz, Cio&#322;kowskiego 2 Street, Lodz 93-510, Poland. magdamalicka@gmail.com.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Witkowska
authors.affiliation: Department of Experimental Hematology of Medical University of Lodz, Cio&#322;kowskiego 2 Street, Lodz 93-510, Poland. majchrzak_agata@o2.pl.|Department of Hematology of Medical University of Lodz, Cio&#322;kowskiego 2 Street, Lodz 93-510, Poland. majchrzak_agata@o2.pl.
authors.forename: Agata
authors.initials: A
authors.lastname: Majchrzak
authors.affiliation: Department of Experimental Hematology of Medical University of Lodz, Cio&#322;kowskiego 2 Street, Lodz 93-510, Poland. barbara_cebula@wp.pl.
authors.forename: Barbara
authors.initials: B
authors.lastname: Cebula-Obrzut
authors.affiliation: Winship Cancer Institute, Emory University School of Medicine, 101 Woodruff Cir, Atlanta, GA 30322, USA. mybonne@emory.edu.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Bonner
authors.affiliation: Department of Hematology of Medical University of Lodz, Cio&#322;kowskiego 2 Street, Lodz 93-510, Poland. robaktad@csk.umed.lodz.pl.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.affiliation: Winship Cancer Institute, Emory University School of Medicine, 101 Woodruff Cir, Atlanta, GA 30322, USA. jarbise@emory.edu.|Atlanta Veterans Administration Hospital, 1670 Clairmont Road, Decatur, GA 30033, USA. jarbise@emory.edu.
authors.forename: Jack L
authors.initials: JL
authors.lastname: Arbiser
authors.affiliation: Department of Experimental Hematology of Medical University of Lodz, Cio&#322;kowskiego 2 Street, Lodz 93-510, Poland. piotr_smolewski@wp.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Smolewski
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism*; D017705:Lignans / Q000494:pharmacology*; D008223:Lymphoma / Q000188:drug therapy / Q000378:metabolism*; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism*; D014320:Triphenylmethyl Compounds / Q000494:pharmacology*; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D001713:Biphenyl Compounds; D017705:Lignans; D014320:Triphenylmethyl Compounds; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C046945:triphenylmethane
keywords: ALL; BL; CLL; DLBCL; MM; honokiol analogues