title: Multifunctional T Lymphocytes Generated After Therapy With an Antitumor Gallotanin-Rich Normalized Fraction Are Related to Primary Tumor Size Reduction in a Breast Cancer Model.
abstract: Natural compounds are promising sources for anticancer therapies because of their multifunctional activity and low toxicity. Although the host immune response (IR) is clearly implicated in tumor control, the relationship between natural therapies and IR has not yet been elucidated. The present work evaluates IR induction after treatment with a gallotannin-rich fraction from Caesalpinia spinosa (P2Et). Breast tumor 4T1 cells were used to evaluate antitumor properties and IR activation. Apoptosis and expression of immunogenic cell death (ICD) markers were assessed in vitro, whereas IR and postvaccination tumor evolution were assessed in vivo. P2Et fraction induced apoptotic cell death, displaying phosphatidylserine externalization and DNA fragmentation. ICD markers such as calreticulin, high-mobility group box 1 translocation from nuclei to cytoplasm, and ATP secretion were observed. Primary tumor control was improved by vaccination with P2Et-pretreated 4T1 cells (t-P2Et), yielding long-lasting ex vivo multifunctional CD4(+) and CD8(+) T lymphocytes (interleukin [IL]-2(+), tumor necrosis factor [TNF]-α(+), interferon [IFN]-γ(+)) that secrete IL-2, TNF-α, IL-4, IL-5, and IFN-γ after specific 4T1 cell stimulation. The present study constitutes the first demonstration of a long-lasting antitumor IR induction and primary tumor reduction induced by a complex natural fraction. These data reveal the potential use of this fraction as an adjuvant in breast cancer treatment.
authors.affiliation: Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Claudia
authors.initials: C
authors.lastname: Urueña
authors.affiliation: Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Gomez
authors.affiliation: Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Tito
authors.initials: T
authors.lastname: Sandoval
authors.affiliation: Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: John
authors.initials: J
authors.lastname: Hernandez
authors.affiliation: University of Macau, Macau, China.
authors.forename: Shaoping
authors.initials: S
authors.lastname: Li
authors.affiliation: Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Barreto
authors.affiliation: Pontificia Universidad Javeriana, Bogotá, Colombia susana.fiorentino@javeriana.edu.co.
authors.forename: Susana
authors.initials: S
authors.lastname: Fiorentino
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D029911:Caesalpinia / Q000737:chemistry*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D006801:Humans; D047348:Hydrolyzable Tannins / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D047348:Hydrolyzable Tannins; D010936:Plant Extracts
keywords: Caesalpinia spinosa; breast cancer; immune response; immunogenic cell death; natural products