title: Antitumor Effects of Systemic DNAse I and Proteases in an In Vivo Model.
abstract: Background Cell-free DNA circulates in cancer patients and induces in vivo cell transformation and cancer progression in susceptible cells. Based on this, we hypothesized that depletion of circulating DNA with DNAse I and a protease mix could have antitumor effects. Study design The study aimed to demonstrate that DNAse I and a protease mix can degrade in vitro DNA and proteins from the serum of healthy individuals and cancer patients, and in vivo in serum of Wistar rats,. Moreover, the antitumor effect of the systemically administered enzyme mix treatmentwas evaluated in nude mice subcutaneously grafted with the human colon cancer cell line SW480. Results The serum DNA of cancer patients or healthy individuals was almost completely degraded in vitro by the enzymatic treatment, but no degradation was found with the enzymes given separately. The intravenous administration of the enzymes led to significant decreases in DNA and proteins from rat serum. No antitumor effect was observed in immunodeficient mice treated with the enzymes given separately. In contrast, the animals that received both enzymes exhibited a marked growth inhibition of tumors, 40% of them having pathological complete response. Conclusion This study demonstrated that systemic treatment with DNAse I and a protease mix in rats decreases DNA and proteins from serum and that this treatment has antitumor effects. Our results support the hypothesis that circulating DNA could have a role in tumor progression, which can be offset by depleting it. Further studies are needed to prove this concept.
authors.affiliation: Instituto Nacional de Cancerología, México City, Mexico.
authors.forename: Catalina
authors.initials: C
authors.lastname: Trejo-Becerril
authors.affiliation: Instituto Nacional de Cancerología, México City, Mexico.
authors.forename: Enrique
authors.initials: E
authors.lastname: Pérez-Cardenas
authors.affiliation: Instituto Nacional de Cancerología, México City, Mexico.
authors.forename: Blanca
authors.initials: B
authors.lastname: Gutiérrez-Díaz
authors.affiliation: Instituto Nacional de Cancerología, México City, Mexico.
authors.forename: Desiree
authors.initials: D
authors.lastname: De La Cruz-Sigüenza
authors.affiliation: Instituto Nacional de Cancerología, México City, Mexico.
authors.forename: Lucía
authors.initials: L
authors.lastname: Taja-Chayeb
authors.affiliation: Instituto Nacional de Cancerología, México City, Mexico.
authors.forename: Mauricio
authors.initials: M
authors.lastname: González-Ballesteros
authors.affiliation: Instituto Nacional de Cancerología, México City, Mexico.
authors.forename: Patricia
authors.initials: P
authors.lastname: García-López
authors.affiliation: Instituto Nacional de Cancerología, México City, Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Chanona
authors.affiliation: Instituto Nacional de Cancerología, México City, Mexico alfonso_duenasg@yahoo.com.|Instituto de InvestigacionesBiomédicas, Universidad Nacional Autónoma de México UNAM/Instituto Nacional de Cancerología, México City, Mexico.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Dueñas-González
mesh_terms: D000328:Adult; D000818:Animals; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D004247:DNA / Q000097:blood; D003850:Deoxyribonuclease I / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D011506:Proteins; D004247:DNA; D003850:Deoxyribonuclease I; D010447:Peptide Hydrolases
keywords: DNAse I; antitumor enzymatic treatment; chymotrypsin; papain; proteases mix; trypsin