title: Modulation of gene expression and cell cycle by botryosphaeran, a (1→3)(1→6)-β-d-glucan in human lymphocytes.
abstract: There is growing interest in the anticancer and immunomodulatory potential of fungal β-d-glucans. In the present study, the modulation of gene expression via RT-qPCR and cell cycle kinetics via flow cytometry were assessed in human normal and tumor (Jurkat) lymphocytes after treatment with botryosphaeran (a fungal (1→3)(1→6)-β-d-glucan) from Botryosphaeria rhodina MAMB-05. Cell cultures were treated with botryosphaeran either alone, or in combination with doxorubicin (DXR), in a post-treatment protocol. The expression of genes involved in immunomodulatory processes, apoptosis and cell cycle control, as well as β-d-glucans cell receptors were assessed. Flow cytometry analysis identified tetraploid Jurkat cells in G1 phase when treated with botryosphaeran combined with DXR. This antiproliferative effect in G1 may be associated with down-regulation of the expression of genes involved in the G1 checkpoint. The repression of the CCR5 gene following botryosphaeran treatment, either alone or in combination with DXR, in tumor lymphocytes indicates a possible affinity of this particular (1→3)(1→6)-β-d-glucan for the receptor CCR5. Therefore, botryosphaeran action appears to be involved in the repression of genes related to the G1 phase of the cell cycle and possibly in the interaction of the botryosphaeran, either alone, or in combination with DXR, with the CCR5 receptor.
authors: Departmento de Biologia Geral, Centro de Ciências Biológicas - Universidade Estadual de Londrina, Londrina - PR, Brazil.
authors: Maressa
authors: M
authors: Malini
authors: Departmento de Biologia Geral, Centro de Ciências Biológicas - Universidade Estadual de Londrina, Londrina - PR, Brazil.
authors: Marilesia Ferreira de
authors: MF
authors: Souza
authors: Departmento de Biologia Geral, Centro de Ciências Biológicas - Universidade Estadual de Londrina, Londrina - PR, Brazil.
authors: Marcelo Tempesta de
authors: MT
authors: Oliveira
authors: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto - SP, Brazil.
authors: Lusânia Maria Greggi
authors: LM
authors: Antunes
authors: Departamento de Ciências Biológicas, Centro de Ciências Fisiológicas - Universidade Federal do Espírito Santo, Vitória - ES, Brazil.
authors: Suely Gomes de
authors: SG
authors: Figueiredo
authors: Departmento de Química, Centro de Ciências Exatas - Universidade Estadual de Londrina, Londrina - PR, Brazil; Biorefining Research Institute, Lakehead University, Thunder Bay, Ontario, Canada P7B 5E1.
authors: Aneli M
authors: AM
authors: Barbosa
authors: Biorefining Research Institute, Lakehead University, Thunder Bay, Ontario, Canada P7B 5E1.
authors: Robert F H
authors: RF
authors: Dekker
authors: Departmento de Biologia Geral, Centro de Ciências Biológicas - Universidade Estadual de Londrina, Londrina - PR, Brazil. Electronic address: ilcecolus@gmail.com.
authors: Ilce Mara de Syllos
authors: IM
authors: Cólus
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005936:Glucans / Q000494:pharmacology*; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D019169:Jurkat Cells; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D005936:Glucans; C483238:botryosphaeran
keywords: Doxorubicin; Fungal β-d-glucan; Human lymphocytes