title: Azadirachta indica exerts chemopreventive action against murine skin cancer: studies on histopathological, ultrastructural changes and modulation of NF-kappaB, AP-1, and STAT1.
abstract: The present study reports the histopathological, ultrastructural changes and modulation of NF-kappaB, AP-1, and STAT 1 during skin carcinogenesis in LACA mice and its intervention with Azadirachta indica. Skin tumors were induced by topical application of 7,12-dimethylbenz(a)anthracene (DMBA) (500 nmol/100 microl for 2 weeks) followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) (1.7 nmol/100 microl of acetone, twice weekly) as a promoter. Male LACA mice were divided into four groups: Control, DMBA/TPA, aqueous Azadirachta indica leaf extract (AAILE), and AAILE + DMBA/TPA. AAILE was administered orally at a dose level of 300 mg/kg body weight three times a week for 20 weeks. Topical application of DMBA/ TPA to the skin resulted in well-developed squamous cell carcinomas characterized by hyperproliferation, hyperkeratosis, and corrugation of the epidermis. Degenerative changes were observed in the tumors of AAILE + DMBA/TPA-treated animals. Scanning electron microscopy revealed surface disruptions and certain rounded structures on the skin tumors of DMBA/TPA-treated animals. Topographical changes were also observed in the tumors of AAILE + DMBA/TPA-treated animals, which resembled regions of degeneration. Tumors obtained in DMBA/TPA group were associated with enhanced expression of NF-kappaB and AP-1 when compared to the control counterparts. Inhibition in tumorigenesis in response to A. indica treatment was accompanied by an overexpression of STAT 1 and AP-1 and decrease in NF-kappaB expression. The results of the present study provide a basis for the chemopreventive potential of A. indica against murine skin carcinogenesis.
authors.affiliation: Department of Biophysics, Basic Medical Sciences Block, Panjab University, Chandigarh, India.
authors.forename: N
authors.initials: N
authors.lastname: Arora
authors.forename: M P
authors.initials: MP
authors.lastname: Bansal
authors.forename: A
authors.initials: A
authors.lastname: Koul
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D031601:Azadirachta; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D050794:STAT1 Transcription Factor / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012878:Skin Neoplasms / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate; D018808:Transcription Factor AP-1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*
chemical_list: D016588:Anticarcinogenic Agents; D016328:NF-kappa B; D010936:Plant Extracts; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D018808:Transcription Factor AP-1; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate