title: Bromelain nanoparticles protect against 7,12-dimethylbenz[a]anthracene induced skin carcinogenesis in mouse model.
abstract: Conventional cancer chemotherapy leads to severe side effects, which limits its use. Nanoparticles (NPs) based delivery systems offer an effective alternative. Several evidences highlight the importance of Bromelain (BL), a proteolytic enzyme, as an anti-tumor agent which however has been limited due to the requirement of high doses at the tumor site. Therefore, we illustrate the development of BL loaded poly (lactic-co-glycolic acid) NPs that show enhanced anti-tumor effects compared to free BL. The formulated NPs with a mean particle size of 130.4 ± 8.81 nm exhibited sustained release of BL. Subsequent investigation revealed enhanced anti-tumor ability of NPs in 2-stage skin tumorigenesis mice model. Reduction in average number of tumors (∼ 2.3 folds), delay in tumorigenesis (∼ 2 weeks), percent tumorigenesis (∼ 4 folds), and percent mortality rate as well as a reduction in the average tumor volume (∼ 2.5 folds) in mice as compared to free BL were observed. The NPs were found to be superior in exerting chemopreventive effects over chemotherapeutic effects at 10 fold reduced dose than free BL, validated by the enhanced ability of NPs (∼ 1.8 folds) to protect the DNA from induced damage. The effects were also supported by histopathological evaluations. NPs were also capable of modulating the expression of pro-apoptotic (P53, Bax) and anti-apoptotic (Bcl2) proteins. Therefore, our findings demonstrate that developed NPs formulation could be used to improve the efficacy of chemotherapy by exerting chemo-preventive effects against induced carcinogenesis at lower dosages.
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Bhatnagar
authors.affiliation: CSIR-Indian Institute of Toxicology Research, Lucknow, India.
authors.forename: Aditya B
authors.initials: AB
authors.lastname: Pant
authors.affiliation: CSIR-Indian Institute of Toxicology Research, Lucknow, India.
authors.forename: Yogeshwer
authors.initials: Y
authors.lastname: Shukla
authors.affiliation: CSIR-Indian Institute of Toxicology Research, Lucknow, India.
authors.forename: Bhushan
authors.initials: B
authors.lastname: Chaudhari
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, Delhi, India; CSIR-Indian Institute of Toxicology Research, Lucknow, India. Electronic address: kcgupta@iitr.res.in.
authors.forename: Kailash C
authors.initials: KC
authors.lastname: Gupta
mesh_terms: D000279:Administration, Cutaneous; D031230:Ananas / Q000737:chemistry; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D001963:Bromelains / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D063646:Carcinogenesis / Q000187:drug effects*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D065546:Drug Liberation; D004355:Drug Stability; D004356:Drug Storage; D004795:Enzyme Stability; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010940:Plant Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D018547:Plant Stems / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011897:Random Allocation; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D016019:Survival Analysis; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D016588:Anticarcinogenic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D010940:Plant Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D001963:Bromelains; C091761:fruit bromelain
keywords: Bromelain; Chemoprevention; DMBA; Nanoparticles; Poly (lactic-co-glycolic acid); Skin tumorigenesis