title: In vitro and in vivo antineoplastic and immunological effects of pterocarpanquinone LQB-118.
abstract: Cancer is a malignancy of worldwide prevalence, and although new therapeutic strategies are under investigation, patients still resort to reductive or palliative chemotherapy. Side effects are a great concern, since treatment can render patients susceptible to infections or secondary cancers. Thus, design of safer chemotherapeutic drugs must consider the risk of immunotoxicity. Pterocarpans are natural isoflavones that possess immunomodulatory and antineoplastic properties. Ubiquitous in nature, quinones are present in chemotherapeutic drugs such as doxorubicin and mitoxantrone. Our group has patented a hybrid molecule, the pterocarpanquinone LQB-118, and demonstrated its antineoplastic effect in vitro. In this report we describe its antineoplastic effect in vivo and assess its toxicity toward the immune system. Treated mice presented no changes in weight of primary and secondary organs of the immune system nor their cellular composition. Immunophenotyping showed that treatment increased CD4(+) thymocytes and proportionally reduced the CD4(+)CD8(+) subpopulation in the thymus. No significant changes were observed in T CD8(+) peripheral lymphocytes nor was the activation of fresh T cells affected after treatment. LQB-118 induced apoptosis in murine tumor cells in vitro, being synergistic with the autophagy promoter rapamycin. Furthermore, treatment significantly reduced ascites or solid Ehrlich and B16F10 melanoma growth in vivo, and ameliorated side effects such as cachexia. Based on its favorable preclinical profile and considering previous results obtained in vitro, this drug emerges as a promising candidate for further development.
authors.affiliation: Laboratory of Tumor Immunology, Leopoldo de Meis Institute of Medical Biochemistry (IBqM), Federal University of Rio de Janeiro (UFRJ), Avenida Carlos Chagas Filho 373, Bloco H, 2° andar sala 003 Cidade Universitária, Rio de Janeiro, RJ, 21941-590, Brazil. salustiano@bioqmed.ufrj.br.|Laboratory of Bioorganic Chemistry, Institute for Natural Products Research, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. salustiano@bioqmed.ufrj.br.
authors.forename: Eduardo J
authors.initials: EJ
authors.lastname: Salustiano
authors.affiliation: Laboratory of Tumor Immunology, Leopoldo de Meis Institute of Medical Biochemistry (IBqM), Federal University of Rio de Janeiro (UFRJ), Avenida Carlos Chagas Filho 373, Bloco H, 2° andar sala 003 Cidade Universitária, Rio de Janeiro, RJ, 21941-590, Brazil.
authors.forename: Matheus L
authors.initials: ML
authors.lastname: Dumas
authors.affiliation: Laboratory of Tumor Immunology, Leopoldo de Meis Institute of Medical Biochemistry (IBqM), Federal University of Rio de Janeiro (UFRJ), Avenida Carlos Chagas Filho 373, Bloco H, 2° andar sala 003 Cidade Universitária, Rio de Janeiro, RJ, 21941-590, Brazil.
authors.forename: Gabriel G
authors.initials: GG
authors.lastname: Silva-Santos
authors.affiliation: Laboratory of Bioorganic Chemistry, Institute for Natural Products Research, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.|Laboratory of Chemistry, Macaé Institute of Metrology and Technology, Federal University of Rio de Janeiro, Professor Aloísio Teixeira Macaé Campus, Macaé, RJ, Brazil.
authors.forename: Chaquip D
authors.initials: CD
authors.lastname: Netto
authors.affiliation: Laboratory of Bioorganic Chemistry, Institute for Natural Products Research, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Paulo R R
authors.initials: PR
authors.lastname: Costa
authors.affiliation: Laboratory of Tumor Immunology, Leopoldo de Meis Institute of Medical Biochemistry (IBqM), Federal University of Rio de Janeiro (UFRJ), Avenida Carlos Chagas Filho 373, Bloco H, 2° andar sala 003 Cidade Universitária, Rio de Janeiro, RJ, 21941-590, Brazil.
authors.forename: Vivian M
authors.initials: VM
authors.lastname: Rumjanek
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008810:Mice, Inbred C57BL; D009285:Naphthoquinones / Q000494:pharmacology / Q000627:therapeutic use; D036343:Pterocarpans / Q000494:pharmacology / Q000627:therapeutic use; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C569361:LQB 118; D009285:Naphthoquinones; D036343:Pterocarpans
keywords: Autophagy; Ehrlich tumor; Immunotoxicity; Melanoma; Naphthoquinone; Pterocarpan