title: Role of cystathionine β-synthase in human breast Cancer.
abstract: Cystathionine β-synthase (CBS) is an enzyme in the transulfuration pathway that can catalyze the condensation of homocysteine (Hcy) and cysteine (Cys) to hydrogen sulfide (H2S) and cystathionine (CTH). CBS-derived H2S is important in angiogenesis and drug resistance in colon and ovarian cancers, respectively. However, the mechanisms by which cancer cell-derived H2S is utilized by cancer cells as a protective agent against host-derived activated macrophages are not yet investigated. This study investigated the mechanistic role of CBS-derived H2S in the protection of human breast cancer (HBC) cells against activated macrophages. HBC patient-derived tissue arrays and immunoblot analysis of HBC cells exhibited significantly increased levels of CBS when compared with their normal counterparts. This was associated with increased levels of H2S and CTH. Silencing of CBS in HBC cells caused a significant decrease in the levels of H2S and CTH but did not affect the growth of these cells per se, in in vitro cultures. However CBS-silenced cells exhibited significantly reduced growth in the presence of activated macrophages and in xenograft models. This was associated with an increase in the steady state levels of reactive aldehyde-derived protein adducts. Exogenous addition of H2S countered the effects of CBS silencing in the presence of macrophages. Conversely overexpression of CBS in human breast epithelial (HBE) cells (which do not naturally express CBS) protected them from activated macrophages, which were otherwise susceptible to the latter.
authors.affiliation: Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA 90095, USA; The Jonsson Cancer Center, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA 90095, USA. Electronic address: ssen@mednet.ucla.edu.
authors.forename: Suvajit
authors.initials: S
authors.lastname: Sen
authors.affiliation: Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Kawahara
authors.affiliation: Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Divya
authors.initials: D
authors.lastname: Gupta
authors.affiliation: Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Tsai
authors.affiliation: Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Marine
authors.initials: M
authors.lastname: Khachatryan
authors.affiliation: Department of Pathology at MD Anderson School of Medicine, Houston, TX 77054, USA.
authors.forename: Sinchita
authors.initials: S
authors.lastname: Roy-Chowdhuri
authors.affiliation: Pathology and Laboratory Medicine at Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Shikha
authors.initials: S
authors.lastname: Bose
authors.affiliation: Semel Institute for Neuroscience and Human Behavior at University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Yoon
authors.affiliation: The Jonsson Cancer Center, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA 90095, USA; Semel Institute for Neuroscience and Human Behavior at University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Kym
authors.initials: K
authors.lastname: Faull
authors.affiliation: Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Farias-Eisner
authors.affiliation: Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA 90095, USA; The Jonsson Cancer Center, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA 90095, USA; Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Gautam
authors.initials: G
authors.lastname: Chaudhuri
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D002462:Cell Membrane / Q000201:enzymology; D018920:Coculture Techniques; D003541:Cystathionine beta-Synthase / Q000502:physiology*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D008264:Macrophages / Q000276:immunology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation
chemical_list: D003541:Cystathionine beta-Synthase; D005978:Glutathione; D006862:Hydrogen Sulfide
keywords: 4-Hydroxynonenal; Breast cancer; Cystathionine β-synthase; Hydrogen sulfide