title: Sesamol Induces Apoptosis by Altering Expression of Bcl-2 and Bax Proteins and Modifies Skin Tumor Development in Balb/c Mice.
abstract: BACKGROUND
  Chemoprevention using natural agents has emerged as a new and promising strategy for reducing cancer burden. Sesamol, a water soluble lignin, is a potent antioxidant with potential anticancer activities. Its small size (molecular weight: 138.34g) coupled with easy permeability (log P: 1.29) results in its excessive systemic loss therefore, compromising local bioavailability. Furthermore, irritant nature of sesamol limits its application on skin per se.
  
  
  OBJECTIVE
  Present study aims to evaluate chemopreventive efficacy of free and encapsulated (SLNs) sesamol, at gross and molecular level, in DMBA induced skin cancer animal model.
  
  
  METHODS
  Evaluation is done in terms of tumor burden quantification, histological evaluation of skin, determination of oxidative stress, and quantification of apoptotic proteins, bcl-2 and bax, using both western blot analysis and immunofluorescence studies.
  
  
  RESULTS
  Sesamol administration (both in free and encapsulated form) significantly decreased the tumor burden and lipid peroxidation level and increased anti-oxidant levels, thereby hampering the development and promotion of skin tumors. Further, downregulation of bcl-2 and stimulation of bax protein expression on treatment with both free and encapsulated sesamol was responsible for the induction of apoptosis in tumor cells. Encapsulating sesamol into SLNs not only reduced its irritant nature which limits its direct topical application but also improved its local targeting to skin.
  
  
  CONCLUSIONS
  Both free and encapsulated sesamol demonstrated the inhibition of tumor progression by inducing skin cell apoptosis via bcl-2/bax mediated pathway.
authors.affiliation: Department of Biophysics, Panjab University, Chandigarh, India.
authors.forename: Rishi
authors.initials: R
authors.lastname: Bhardwaj
authors.affiliation: Department of Biophysics, Panjab University, Chandigarh, India.
authors.forename: S N
authors.initials: SN
authors.lastname: Sanyal
authors.affiliation: Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Kim
authors.initials: K
authors.lastname: Vaiphei
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
authors.forename: Vandita
authors.initials: V
authors.lastname: Kakkar
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
authors.forename: Parneet Kaur
authors.initials: PK
authors.lastname: Deol
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC Centre for Advance Study, Panjab University, Chandigarh-160014, India.
authors.forename: Indu Pal
authors.initials: IP
authors.lastname: Kaur
authors.affiliation: Department of Chemistry and Biochemistry, University of Windsor, Windsor, N9B 3P4 ON, Canada.
authors.forename: Tranum
authors.initials: T
authors.lastname: Kaur
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D052117:Benzodioxoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D010636:Phenols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013329:Structure-Activity Relationship; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis*
chemical_list: D000970:Antineoplastic Agents; D052117:Benzodioxoles; D010636:Phenols; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C025583:sesamol
keywords: Chemoprevention; SLNs; antioxidant; apoptosis; apoptotic proteins