Enhanced percutaneous delivery of 1,1-bis(3′-indolyl)-1-(p-chlorophenyl) methane for skin cancer chemoprevention

Cedar H.A. Boakye, Punit P. Shah, Ravi Doddapaneni, Apurva R. Patel, Stephen Safe, Mandip Singh

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Skin cancer has high incidence in the United States and is mainly caused by ultraviolet B (UVB) radiation. In this study, we demonstrated the role of 1,1-bis(3′-indolyl)-1-(p-chlorophenyl) methane (DIM-D) in the prevention of skin photocarcinogenesis using an in vivo UVB-induced skin cancer model. We also evaluated the efficiency of oleic acid-modified nanostructured lipid carriers to deliver DIM-D across the skin barrier into the epidermis for chemopreventive activity. Nanocarriers were 203.00±21.21 nm in diameter with polydispersity, zeta potential and entrapment efficiency of 0.33±0.01, 37.17±0.90 mV and 93.64±0.65%, respectively. Oleic acid-modified nanocarriers were incorporated into Hydroxypropyl methylcellulose to form DIM-D-Nanogel (DIM-D-N). DIM-D-N pretreatment prior to UVB exposure delayed tumor initiation and reduced tumor multiplicity (p < 0005) at the end of the study compared to Epigallocatechin gallate (EGCG) gel pretreatment. DIM-D-N pretreatment decreased UVB-induced damage to skin lipids and proteins (p<0..05), respectively by 7.63 and 2.56-fold less than EGCG gel pretreatment and by 17.86 and 11.92-fold less than UVB-only treatment. Histology showed rete-ridge extension, epidermal thickening and hyperkeratosis for UVB-only treatment and EGCG gel pretreatment; DIM-D-N pretreatment showed similar features as the negative control. Western blot analysis showed increased Nurr1 expression (p<0.05) for DIM-D-N pretreated group compared to EGCG gel (4.68-fold). DIM-D-N pretreatment reduced BCl-2 expression (p<0..05) but increased Bax and cPARP. Knock down studies with Nurr1 siRNA reduced the expressions of Nurr1 and cPARP by 8.18 and 1.45-fold, respectively (p<0.05). Our results suggest the role of DIM-D in skin cancer chemoprevention mediated by possible molecular therapeutic targets such as Nurr1.

Original languageEnglish (US)
Pages (from-to)1269-1281
Number of pages13
JournalJournal of Biomedical Nanotechnology
Volume11
Issue number7
DOIs
StatePublished - Jul 1 2015

Keywords

  • 1,1-bis(3′-indolyl)-1-(p-chlorophenyl) Methane (DIM-D)
  • 3,3′-Diindolylmethane (DIM)
  • DIM-D nanogel (DIM-D-N)
  • Epigallocatechin gallate (EGCG)
  • Glutathione depletion
  • Lipid peroxidation
  • Nanostructured lipid carriers (NLC)
  • Oleic acid surface modified NLC (NLC-OA)
  • Protein carbonylation
  • Skin cancer chemoprevention
  • Ultraviolet B (UVB) radiation

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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