title: Human breast adenocarcinoma cytotoxicity and modulation of 7,12-dimethylbenz[a]anthracene-induced mammary carcinoma in Balb/c mice by Acacia catechu (L.f.) Wild heartwood.
abstract: OBJECTIVE
  The chemopreventive potential of (+)-catechin-rich extract of Acacia catechu (L.f.) Willd. heartwood (AQCE) was evaluated against human breast adenocarcinoma cell line (MCF-7) and 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinoma in Balb/c mice.
  
  
  METHODS
  Cell cytotoxicity was investigated using different colorimetric assays. Apoptosis was observed using diphenylamine assay and fluorescent microscopy. AQCE was further evaluated for antitumor activity against DMBA-induced mammary carcinoma. The levels of tumor markers and oxidative stress were measured. Furthermore, level of transcription factors was measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The results showed that administration of AQCE showed a dose-dependent growth inhibition response and DNA fragmentation in MCF-7 cells. Tumor multiplicity was significantly decreased to 42.91% with AQCE when compared with DMBA-treated animals. The levels of tumor markers such as total sialic acid and lipid-associated sialic acid were substantially increased after DMBA treatment. However, AQCE treatment restored tumor markers level. AQCE also significantly reduced elevated levels of nitrite and malondialdehyde in DMBA-treated animals. Additionally, AQCE also increased the activities of antioxidant enzymes, viz., catalase, superoxide dismutase, total thiol, reduced glutathione, protein thiol, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase in the mammary tissue and liver mitochondria of DMBA-administered animals. Significant increase in the protein levels of p53, c-jun, and p65 were observed in DMBA-treated mice, whereas less expression was observed in AQCE-treated animals. Eventually, AQCE also significantly improved body weight and maintained the mammary tissue architecture in normal range.
  
  
  CONCLUSIONS
  The present data strongly suggest that anticancer potentiality of (+)-catechin-rich AQCE may be attributable to its ability to positively modulate tumor markers as well as the antioxidant system that could decompose the peroxides and, thereby, offer a protection against lipid peroxidation and linked to the expression of transcription factors during DMBA-induced mammary carcinoma.
authors.affiliation: Jaypee University of Information Technology, Waknaghat, Himachal Pradesh, India.
authors.forename: Jitender
authors.initials: J
authors.lastname: Monga
authors.forename: Chetan Singh
authors.initials: CS
authors.lastname: Chauhan
authors.forename: Manu
authors.initials: M
authors.lastname: Sharma
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000045:Acacia; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D015127:9,10-Dimethyl-1,2-benzanthracene
keywords: AP-1; Acacia catechu; NF-κB; cytotoxicity; oxidative stress; p53; tumor markers